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Search Results (519)

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Keywords = cell motility and invasion

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26 pages, 7715 KiB  
Article
Harnessing Nature’s Chemistry: Deciphering Olive Oil Phenolics for the Control of Invasive Breast Carcinoma
by Nehal A. Ahmed, Abu Bakar Siddique, Afsana Tajmim, Judy Ann King and Khalid A. El Sayed
Molecules 2025, 30(15), 3157; https://doi.org/10.3390/molecules30153157 - 28 Jul 2025
Viewed by 353
Abstract
Breast cancer (BC) is the most common malignancy and the second-leading cause of cancer-related mortalities in women. Epidemiological studies suggested the reduced BC incidence in Mediterranean populations due to the daily consumption of diets rich in extra-virgin olive oil (EVOO). EVOO secoiridoid phenolics [...] Read more.
Breast cancer (BC) is the most common malignancy and the second-leading cause of cancer-related mortalities in women. Epidemiological studies suggested the reduced BC incidence in Mediterranean populations due to the daily consumption of diets rich in extra-virgin olive oil (EVOO). EVOO secoiridoid phenolics are widely known for their positive outcomes on multiple cancers, including BC. The current study investigates the suppressive effects of individual and combined EVOO phenolics for BC progression and motility. Screening of a small library of EVOO phenolics at a single dose of 10 µM against the viability of the BC cell lines ZR-75-1 (luminal A) and MDA-MB-231 (triple negative BC, TNBC) identified oleocanthal (OC) and ligstroside aglycone (LA) as the most active hits. Screening of EVOO phenolics for BC cells migration inhibition identified OC, LA, and the EVOO lignans acetoxypinoresinol and pinoresinol as the most active hits. Combination studies of different olive phenolics showed that OC combined with LA had the best synergistic inhibitory effects against the TNBC MDA-MB-231 cells migration. A combination of 5 µM of each of OC and LA potently suppressed the migration and invasion of the MDA-MB-231 cells versus LA and OC individual therapies and vehicle control (VC). Animal studies using the ZR-75-1 BC cells orthotopic xenografting model in female nude mice showed significant tumor progression suppression by the combined OC-LA, 5 mg/kg each, ip, 3X/week treatments compared to individual LA and OC treatments and VC. The BC suppressive effects of the OC-LA combination were associated with the modulation of SMYD2–EZH2–STAT3 signaling pathway. A metastasis–clonogenicity animal study model using female nude mice subjected to tail vein injection of MDA-MB-231-Luc TNBC cells also revealed the effective synergy of the combined OC-LA, 5 mg/kg each, compared to their individual therapies and VC. Thus, EVOO cultivars rich in OC with optimal LA content can be useful nutraceuticals for invasive hormone-dependent BC and TNBC progression and metastasis. Full article
(This article belongs to the Special Issue Bioactive Molecules in Foods: From Sources to Functional Applications)
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26 pages, 1785 KiB  
Review
Targeting RHAMM in Cancer: Crosstalk with Non-Coding RNAs and Emerging Therapeutic Strategies Including Peptides, Oligomers, Antibodies, and Vaccines
by Dong Oh Moon
Int. J. Mol. Sci. 2025, 26(15), 7198; https://doi.org/10.3390/ijms26157198 - 25 Jul 2025
Viewed by 196
Abstract
Cancer remains a major cause of mortality worldwide, driven by complex molecular mechanisms that promote metastasis and resistance to therapy. Receptor for hyaluronan-mediated motility (RHAMM) has emerged as a multifunctional regulator in cancer, contributing to cell motility, invasion, proliferation, and fibrosis. In addition [...] Read more.
Cancer remains a major cause of mortality worldwide, driven by complex molecular mechanisms that promote metastasis and resistance to therapy. Receptor for hyaluronan-mediated motility (RHAMM) has emerged as a multifunctional regulator in cancer, contributing to cell motility, invasion, proliferation, and fibrosis. In addition to being regulated by non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, RHAMM serves as a promising therapeutic target. Recent developments in RHAMM-targeted strategies include function-blocking peptides (e.g., NPI-110, NPI-106, and P15-1), hyaluronan (HA) oligomers, and anti-RHAMM antibodies, all shown to modulate tumor stroma and suppress tumor invasiveness. Importantly, RHAMM-targeted peptide vaccines, such as the RHAMM-R3 epitope, have demonstrated immunogenicity and anti-leukemia efficacy in both pre-clinical and early clinical studies, suggesting their potential to elicit specific CD8+ T-cell responses and enhance graft-versus-leukemia effects. This review summarizes the intricate roles of RHAMM in cancer progression, its modulation by ncRNAs, and the translational promise of novel RHAMM-targeting approaches, providing insights into future directions for precision cancer therapy. Full article
(This article belongs to the Section Molecular Oncology)
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16 pages, 2877 KiB  
Article
Functional Disruption of IQGAP1 by Truncated PALB2 in Two Cases of Breast Cancer: Implications for Proliferation and Invasion
by Natalia-Dolores Pérez-Rodríguez, Rita Martín-Ramírez, Rebeca González-Fernández, María del Carmen Maeso, Julio Ávila and Pablo Martín-Vasallo
Biomedicines 2025, 13(8), 1804; https://doi.org/10.3390/biomedicines13081804 - 23 Jul 2025
Viewed by 402
Abstract
Background/Objectives: Truncating mutations in PALB2, a critical component of the BRCA1-PALB2-BRCA2 homologous recombination repair complex, are associated with increased risk and aggressiveness of breast cancer. The consequences of PALB2 truncation on the expression, localization, and functional dynamics of the scaffold protein IQGAP1 [...] Read more.
Background/Objectives: Truncating mutations in PALB2, a critical component of the BRCA1-PALB2-BRCA2 homologous recombination repair complex, are associated with increased risk and aggressiveness of breast cancer. The consequences of PALB2 truncation on the expression, localization, and functional dynamics of the scaffold protein IQGAP1 were investigated in this study based on two cases of truncated PALB2 human breast invasive ductal carcinoma (IDC), specifically, c.1240C>T (p.Arg414*) and c.2257C>T (p.Arg753*). Methods: Using confocal microscopy, we examined co-expression patterns of IQGAP1 with PALB2, PCNA, CK7, and β-tubulin in tumor tissues from both control cancer and PALB2-mutated cases. Results: In PALB2-truncated tumors, IQGAP1 exhibited enhanced peripheral and plasma membrane localization with elevated co-localization levels compared to controls, suggesting altered cytoskeletal organization. PALB2 truncation increased nuclear and cytoplasmic N-terminal PALB2 immunoreactivity, indicating the presence of truncated isoforms disrupting the homologous recombination repair system. Co-expression analyses with PCNA revealed an inverse expression pattern between IQGAP1 and proliferation markers, suggesting S-phase cell cycle-dependent heterogeneity. Furthermore, the loss of IQGAP1 dominance over CK7 and β-tubulin in mutant tumors, along with persistent intercellular spacing, implied a loss of cell–cell cohesion and the acquisition of invasive traits. Conclusions: These data support a model where PALB2 truncation triggers a reorganization of IQGAP1 that disrupts its canonical structural functions and facilitates tumor progression via enhanced motility and impaired cell–cell interaction. IQGAP1 thus serves as both a functional effector and potential biomarker in PALB2-mutated IDC, opening novel paths for diagnosis and targeted therapeutic intervention. Full article
(This article belongs to the Section Cancer Biology and Oncology)
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18 pages, 3377 KiB  
Article
The Virulence Factor LLO of Listeria monocytogenes Can Hamper Biofilm Formation and Indirectly Suppress Phage-Lytic Effect
by Banhong Liu, Mei Bai, Wuxiang Tu, Yanbin Shen, Jingxin Liu, Zhenquan Yang, Hongduo Bao, Qingli Dong, Yangtai Liu, Ran Wang, Hui Zhang and Liangbing Hu
Foods 2025, 14(15), 2554; https://doi.org/10.3390/foods14152554 - 22 Jul 2025
Viewed by 293
Abstract
Listeria monocytogenes is a life-threatening bacterial foodborne pathogen that can persist in food-processing facilities for years. Although phages can control L. monocytogenes during food production, phage-resistant bacterial subpopulations can regrow in phage-treated environments. In this study, an L. monocytogenes hly defective strain, NJ05-Δ [...] Read more.
Listeria monocytogenes is a life-threatening bacterial foodborne pathogen that can persist in food-processing facilities for years. Although phages can control L. monocytogenes during food production, phage-resistant bacterial subpopulations can regrow in phage-treated environments. In this study, an L. monocytogenes hly defective strain, NJ05-Δhly, was produced, which considerably regulated the interactions between L. monocytogenes and phages. Specifically, we observed a 76.92-fold decrease in the efficiency of plating of the defective strain following infection with the Listeria phage vB-LmoM-NJ05. The lytic effect was notably diminished at multiplicities of infection of 1 and 10. Furthermore, the inactivation of LLO impaired biofilm formation, which was completely suppressed and eliminated following treatment with 108 PFU/mL of phage. Additionally, phages protected cells from mitochondrial membrane damage and the accumulation of mitochondrial reactive oxygen species induced by L. monocytogenes invasion. Transcriptomic analysis confirmed these findings, revealing the significant downregulation of genes associated with phage sensitivity, pathogenicity, biofilm formation, and motility in L. monocytogenes. These results underscore the vital role of LLO in regulating the pathogenicity, phage susceptibility, and biofilm formation of L. monocytogenes. These observations highlight the important role of virulence factors in phage applications and provide insights into the potential use of phages for developing biosanitizers. Full article
(This article belongs to the Special Issue Biofilm Formation and Control in the Food Industry)
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25 pages, 3835 KiB  
Article
A Marine-Derived Steroid from Rhodococcus sp., 3,12-Dioxochola-4,6-dien-24-oic Acid, Enhances Skin Re-Epithelialization and Tissue Repair
by Mücahit Varlı, Hui Tan, Chaeyoung Lee, Jeongyun Lee, Ji Young Lee, Jeong-Hyeon Kim, Songyi Lee, Hangun Kim and Sang-Jip Nam
Mar. Drugs 2025, 23(7), 292; https://doi.org/10.3390/md23070292 - 19 Jul 2025
Viewed by 522
Abstract
The discovery of bioactive natural compounds from microbes holds promise for regenerative medicine. In this study, we identified and characterized a steroid-like compound, 3,12-dioxochola-4,6-dien-24-oic acid (DOCDA), from a crude extract of Rhodococcus sp. DOCDA significantly promoted wound healing by enhancing HaCaT cell invasion [...] Read more.
The discovery of bioactive natural compounds from microbes holds promise for regenerative medicine. In this study, we identified and characterized a steroid-like compound, 3,12-dioxochola-4,6-dien-24-oic acid (DOCDA), from a crude extract of Rhodococcus sp. DOCDA significantly promoted wound healing by enhancing HaCaT cell invasion and migration. It upregulated key growth factors (EGF, VEGF-A, IGF, TGF-β, and HGF), indicating the activation of regenerative signaling. Additionally, DOCDA increased the expression of genes related to focal adhesion and cytoskeletal regulation (ITGB1, ITGA4, FAK, SRC, RHOA, CDC42, RAC1, and paxillin), supporting enhanced cellular motility and remodeling. Notably, DOCDA promoted stem-like properties in HaCaT cells, as shown by increased spheroid formation and elevated levels of the stemness markers ALDH1 and CD44. Target prediction and molecular docking identified the glucocorticoid receptor (GR) as the primary target of DOCDA, with a docking score of −7.7 kcal/mol. Network and pathway enrichment analysis revealed that GR-linked pathways were significantly associated with wound healing, including steroid hormone signaling, inflammation, immune responses, and cell migration. In vivo, the topical application of DOCDA led to over 70% wound closure in mice by day 5. These findings suggest that DOCDA is a steroid-like compound that accelerates wound healing and may serve as a potential agent in regenerative therapy. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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14 pages, 470 KiB  
Review
Unraveling the Role of the microRNA-Mediated Regulation of Actin-Binding Proteins in Ovarian Cancer: A Narrative Review
by Efthalia Moustakli, Anastasios Potiris, Athanasios Zikopoulos, Apostolia Galani, Konstantinos Kechagias, Grigorios Karampas, Ismini Anagnostaki, Chrysi Christodoulaki, Angeliki Gerede, Panagiotis Christopoulos, Nikolaos Thomakos and Sofoklis Stavros
Cancers 2025, 17(14), 2315; https://doi.org/10.3390/cancers17142315 - 11 Jul 2025
Viewed by 285
Abstract
Ovarian cancer remains one of the most lethal gynecological malignancies, primarily due to its late diagnosis and limited prospects for successful treatment. MiRNAs have been shown to be important post-transcriptional regulators in a variety of cancer-related pathways in recent years. One of the [...] Read more.
Ovarian cancer remains one of the most lethal gynecological malignancies, primarily due to its late diagnosis and limited prospects for successful treatment. MiRNAs have been shown to be important post-transcriptional regulators in a variety of cancer-related pathways in recent years. One of the principal mechanisms underlying the motility, invasiveness, and metastatic potential of ovarian cancer cells is the microRNA-mediated regulation of ABPs. As integral components of the cytoskeletal network, ABPs participate in dynamic cellular processes such as migration, adhesion, and invasion, and are critically involved in tumor development and progression. Recent data indicate that some miRNAs affect ABP expression and activity, which in turn affects cytoskeletal remodeling and, ultimately, tumor cell behavior. The role of miRNAs in cancer development is inherently complex due to their ability to function as both tumor suppressors and oncogenes, depending on the molecular context. Key ABPs that are targeted by particular miRNAs are discussed in terms of their clinical relevance, including their potential utility as diagnostic biomarkers or therapeutic targets. A deeper understanding of these regulatory pathways may offer new opportunities for early detection and personalized treatment strategies. In this narrative review, the current knowledge of how miRNAs affect ABP expression and function, and how this interaction contributes to the development and progression of ovarian cancer, is compiled. Full article
(This article belongs to the Special Issue The Role of Actin Binding Proteins in Cancer Progression)
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22 pages, 3822 KiB  
Article
Human Extravillous Trophoblasts Require SRC-2 for Sustained Viability, Migration, and Invasion
by Vineet K. Maurya, Pooja Popli, Bryan C. Nikolai, David M. Lonard, Ramakrishna Kommagani, Bert W. O’Malley and John P. Lydon
Cells 2025, 14(13), 1024; https://doi.org/10.3390/cells14131024 - 4 Jul 2025
Viewed by 486
Abstract
Defective placentation is a recognized etiology for several gestational complications that include early pregnancy loss, preeclampsia, and intrauterine growth restriction. Sustained viability, migration, and invasion are essential cellular properties for embryonic extravillous trophoblasts to execute their roles in placental development and function, while [...] Read more.
Defective placentation is a recognized etiology for several gestational complications that include early pregnancy loss, preeclampsia, and intrauterine growth restriction. Sustained viability, migration, and invasion are essential cellular properties for embryonic extravillous trophoblasts to execute their roles in placental development and function, while derailment of these cellular processes is linked to placental disorders. Although the cellular functions of extravillous trophoblasts are well recognized, our understanding of the pivotal molecular determinants of these functions is incomplete. Using the HTR-8/SVneo immortalized human extravillous trophoblast cell line, we report that steroid receptor coactivator-2 (SRC-2), a coregulator of transcription factor-mediated gene expression, is essential for extravillous trophoblast cell viability, motility, and invasion. Genome-scale transcriptomics identified an SRC-2-dependent transcriptome in HTR-8/SVneo cells that encodes a diverse spectrum of proteins involved in placental tissue development and function. Underscoring the utility of this transcriptomic dataset, we demonstrate that WNT family member 9A (WNT 9A) is not only regulated by SRC-2 but is also crucial for maintaining many of the above SRC-2-dependent cellular functions of human extravillous trophoblasts. Full article
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25 pages, 1270 KiB  
Review
Biofilm Formation of Pseudomonas aeruginosa in Cystic Fibrosis: Mechanisms of Persistence, Adaptation, and Pathogenesis
by Dayana Borisova, Tsvetelina Paunova-Krasteva, Tanya Strateva and Stoyanka Stoitsova
Microorganisms 2025, 13(7), 1527; https://doi.org/10.3390/microorganisms13071527 - 30 Jun 2025
Viewed by 791
Abstract
Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting a large number of individuals in Europe. The disease arises from mutations in the CFTR gene encoding the cystic fibrosis transmembrane conductance regulator, a chloride ion channel crucial for maintaining epithelial ion and [...] Read more.
Cystic fibrosis (CF) is a life-limiting autosomal recessive disorder affecting a large number of individuals in Europe. The disease arises from mutations in the CFTR gene encoding the cystic fibrosis transmembrane conductance regulator, a chloride ion channel crucial for maintaining epithelial ion and fluid homeostasis. Dysfunctional CFTR disrupts mucociliary clearance, particularly in the respiratory tract, resulting in persistent bacterial colonization, chronic inflammation, and progressive pulmonary damage—ultimately leading to respiratory failure, the principal cause of mortality in CF patients. Early diagnosis and advances in therapy have substantially improved both survival and quality of life. A hallmark of CF pathology is the establishment of polymicrobial infections within the thickened airway mucus. Pseudomonas aeruginosa is the dominant pathogen in chronic CF lung infections and demonstrates a remarkable capacity for adaptation via biofilm formation, metabolic reprogramming, and immune evasion. Biofilms confer increased tolerance to antimicrobial agents and facilitate long-term persistence in hypoxic, nutrient-limited microenvironments. P. aeruginosa exhibits a wide range of virulence factors, including exotoxins (e.g., ExoU, ExoS), pigments (pyoverdine, pyochelin), and motility structures (flagella and pili), which contribute to tissue invasion, immune modulation, and host damage. During chronic colonization, P. aeruginosa undergoes significant genotypic and phenotypic changes, such as mucoid conversion, downregulation of acute virulence pathways, and emergence of hypermutator phenotypes that facilitate rapid adaptation. Persistent cells, a specialized subpopulation characterized by metabolic dormancy and antibiotic tolerance, further complicate eradication efforts. The dynamic interplay between host environment and microbial evolution underlies the heterogeneity of CF lung infections and presents significant challenges for treatment. Elucidating the molecular mechanisms driving persistence, hypermutability, and biofilm resilience is critical for the development of effective therapeutic strategies targeting chronic P. aeruginosa infections in CF. Full article
(This article belongs to the Section Biofilm)
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24 pages, 2227 KiB  
Review
An Insight into Cancer Cells and Disease Progression Through the Lens of Mathematical Modeling
by Polychronis Michalakis, Dimitra Vasilaki, Ali Jihad Abdallah, Charilaos Asikis, Athina Niakou, Athanasios Stratos, Alexandros Tsouknidas, Elaine Johnstone and Konstantinos Michalakis
Curr. Issues Mol. Biol. 2025, 47(7), 477; https://doi.org/10.3390/cimb47070477 - 20 Jun 2025
Viewed by 476
Abstract
During cancer initiation, normal cells acquire mutations disrupting standard cellular processes, activating oncogenes and inactivating tumor suppressor genes, acquiring the well-described hallmarks of cancer on the path to malignancy. This process is influenced by a combination of physiological and metabolic pathways, as well [...] Read more.
During cancer initiation, normal cells acquire mutations disrupting standard cellular processes, activating oncogenes and inactivating tumor suppressor genes, acquiring the well-described hallmarks of cancer on the path to malignancy. This process is influenced by a combination of physiological and metabolic pathways, as well as environmental cues, and leads to abnormal cell cycle, increased cell motility, and invasive characteristics. Cancer cell organelles also present some distinct differences from those of normal cells. Cancer progression requires certain tumorigenic biochemical pathways to be activated. However, mechanical cues are also important, as they have an effect on cell differentiation and fate. A continuous biochemical–biomechanical interaction exists, which affects the mechanical properties of the cells, as well as their behavior. This review aims to focus on the mathematical relationships governing cancer mechanobiology and examine how the altered mechanical properties of a cancer cell may affect malignant progression. Full article
(This article belongs to the Section Bioinformatics and Systems Biology)
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51 pages, 1586 KiB  
Review
ECM Mechanics Control Jamming-to-Unjamming Transition of Cancer Cells
by Claudia Tanja Mierke
Cells 2025, 14(13), 943; https://doi.org/10.3390/cells14130943 - 20 Jun 2025
Viewed by 1132
Abstract
Cancer metastasis constitutes a multifactorial phenomenon that continues to confound therapeutic strategies. The biochemical signals governing motile phenotypes have been extensively characterized, but mechanobiological interactions have only recently been integrated into cancer cell motility models and remain less well elucidated. The identification of [...] Read more.
Cancer metastasis constitutes a multifactorial phenomenon that continues to confound therapeutic strategies. The biochemical signals governing motile phenotypes have been extensively characterized, but mechanobiological interactions have only recently been integrated into cancer cell motility models and remain less well elucidated. The identification of the biochemically and mechanically controlled epithelial–mesenchymal transition (EMT) of cancer cells, which occurs either completely or partially, has led to a major breakthrough and a universal phenomenon in cancers. In addition, a relatively new theory based on mechanobiological aspects called “jamming-to-unjamming transition” is being proposed to explain the transition of cancer cells to an invasive phenotype. The latter transition may help to better understand the different types of 3D migration and invasion of cancer cells. Similarly to EMT, the transition from jamming to unjamming seems to be controlled by molecular and physical factors, including cell mechanics and mechanical cues from the extracellular matrix (ECM) of the tumor microenvironment (TME). It is challenging to grasp the distinctions between the transition from jamming to unjamming and EMT, as they appear to be the same at first glance. However, upon closer examination, the two transitions are quite separate. Moreover, it is still unclear whether both transitions may act synergistically. This review highlights the most important breakthroughs in the transition from jamming to unjamming, with a focus on mechanobiology and extracellular environmental aspects, and it compares them with those of EMT. In addition, the impact of the TME, such as ECM scaffold and cancer-associated fibroblasts (CAFs) on the jamming-to-unjamming transition is discussed. Finally, the research frontiers and future directions in the field of mechanobiological research in cancer metastasis are outlined. Full article
(This article belongs to the Special Issue Role of Extracellular Matrix in Cancer and Disease)
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13 pages, 3193 KiB  
Article
HMGB1 as a Key Mediator in Malignant Mesothelioma and a Potential Target for Asbestos-Related Cancer Therapy
by Yi-Fang Zhong, Chan Ding, Chun-Ji Yao, Jia-Chun Wang, Min-Qian Feng, Xiao-Xue Gong, Lin Yu, Hua-Dong Xu and Hai-Ling Xia
Toxics 2025, 13(6), 448; https://doi.org/10.3390/toxics13060448 - 28 May 2025
Viewed by 570
Abstract
Malignant mesothelioma (MM) is a highly aggressive cancer strongly associated with asbestos exposure, and accumulating evidence suggests that high mobility group box 1 (HMGB1) plays a central role in its pathogenesis. Our in vitro and in vivo experiments revealed that HMGB1 was highly [...] Read more.
Malignant mesothelioma (MM) is a highly aggressive cancer strongly associated with asbestos exposure, and accumulating evidence suggests that high mobility group box 1 (HMGB1) plays a central role in its pathogenesis. Our in vitro and in vivo experiments revealed that HMGB1 was highly expressed in MM. Both genetic and pharmacological inhibition of HMGB1 markedly suppressed MM cell viability, migration, and invasion, while inducing G1-phase cell cycle arrest and enhancing apoptosis. Interestingly, the inhibition of Toll-like receptor 4 (TLR4), achieved through both siRNA and TAK-242 treatment, not only suppressed tumor-promoting signals but also reduced HMGB1 expression, suggesting a self-amplifying HMGB1-TLR4 loop. Mechanistically, in vitro experiments indicated that suppression of HMGB1 and TLR4 was associated with decreased activation of NF-κB, AKT, and ERK pathways, which are involved in regulating MM cell survival and motility. In xenograft models, treatment with ethyl pyruvate (EP) and TAK-242 significantly suppressed tumor growth and HMGB1 expression, reinforcing their therapeutic potential. Given HMGB1’s influence on both tumor cell behavior and the immune microenvironment, targeting the HMGB1-TLR4 axis may not only provide a novel therapeutic strategy for MM but also offer insights into the mechanisms underlying asbestos-induced tumorigenesis, potentially guiding future prevention and intervention strategies in asbestos-exposed populations. Full article
(This article belongs to the Special Issue Health Effects of Exposure to Environmental Pollutants—2nd Edition)
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13 pages, 1158 KiB  
Review
The Mechanical Properties of Breast Cancer Cells and Their Surrounding Microenvironment
by Leila Jahangiri
Int. J. Mol. Sci. 2025, 26(11), 5183; https://doi.org/10.3390/ijms26115183 - 28 May 2025
Viewed by 590
Abstract
Breast cancer is a major health concern for women worldwide, and therefore, understanding various changes acquired by breast cancer cells is relevant to a better comprehension of the disease. One such change includes alterations to the mechanical properties of breast cancer cells. For [...] Read more.
Breast cancer is a major health concern for women worldwide, and therefore, understanding various changes acquired by breast cancer cells is relevant to a better comprehension of the disease. One such change includes alterations to the mechanical properties of breast cancer cells. For example, cells with high malignant potential show lower adhesion forces and higher cell deformability. Mechanical forces, including tensile and compressive forces of the cytoskeleton and the extracellular matrix such as integrin, collagen, and the basement membrane, can affect BC cells. These forces alter the properties of cancer cells, drive them towards invasiveness due to different motility and proliferative profiles, and change their microenvironment. This study will focus on the mechanical characteristics of breast cancer cells and the extracellular matrix. Furthermore, changes induced in breast cancer cells following exposure to mechanical forces will be reviewed. Genes that link phenotype to mechanical forces and the implications of these forces for diagnostics and treatment will be discussed. Full article
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39 pages, 20360 KiB  
Article
Chondrosarcoma: Multi-Targeting Therapeutic Effects of Doxorubicin, BEZ235, and the Small Molecule Aspartyl-Asparaginyl-β-hydroxylase Inhibitor SMI1182
by Megan Fife, Ming Tong, Bhaskar Das, Rene Rodriguez, Parthiban Chokkalingam, Rolf I. Carlson and Suzanne M. de la Monte
Cancers 2025, 17(10), 1671; https://doi.org/10.3390/cancers17101671 - 15 May 2025
Viewed by 659
Abstract
Background/Objectives: Chondrosarcoma (CS), the most common malignant bone tumor in adults, exhibits a poor prognosis due to high rates of post-surgical recurrence and metastasis, and resistance to chemotherapy. CS’s abundant expression of aspartyl-asparaginyl-β-hydroxylase (ASPH), which drives invasive tumor growth via Notch and PI3K/mTOR [...] Read more.
Background/Objectives: Chondrosarcoma (CS), the most common malignant bone tumor in adults, exhibits a poor prognosis due to high rates of post-surgical recurrence and metastasis, and resistance to chemotherapy. CS’s abundant expression of aspartyl-asparaginyl-β-hydroxylase (ASPH), which drives invasive tumor growth via Notch and PI3K/mTOR activation, opens opportunities for treatment in combination with standard Doxorubicin (DOX) chemotherapy. We hypothesized that the small molecule inhibitor SMI1182, which targets the catalytic domain of ASPH, and BEZ235, which targets PI3K/mTOR, could enhance the chemotherapeutic effects of DOX. Human CS1 (Grade 3) and CDS11 (Grade 2) conventional CS cell lines were treated with broad dose ranges of DOX, BEZ235, or SMI1182 as mono- or combination therapy to assess their anti-tumor effects on cell viability, toxicity, and motility. Methods: Mechanistic studies included the analysis of ASPH expression, Notch signaling, and insulin/IGF/IRS pathway activation through mTOR. DOX, BEZ235, or SMI1182 treatments caused dose-dependent cell loss and cytotoxicity. Results: SMI1182 and BEZ235, with or without DOX, significantly reduced directional motility. Combined treatments had additive cytotoxic effects linked to the reduced expression of ASPH, Notch transcription factors, and insulin receptor substrate type I, which positively regulates both ASPH and Notch. Conclusions: Triple-drug treatment with DOX, SMI1182, and BEZ235 could potentially improve disease-free survival with CS by the simultaneous targeting of multiple upstream mediators of aggressive malignant tumor cell behavior. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Cancer Treatment)
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26 pages, 1178 KiB  
Review
The Role of Ion Channels in Cervical Cancer Progression: From Molecular Biomarkers to Diagnostic and Therapeutic Innovations
by Elżbieta Bartoszewska, Melania Czapla, Katarzyna Rakoczy, Michał Filipski, Katarzyna Rekiel, Izabela Skowron, Julita Kulbacka and Christopher Kobierzycki
Cancers 2025, 17(9), 1538; https://doi.org/10.3390/cancers17091538 - 1 May 2025
Cited by 1 | Viewed by 756
Abstract
Ion channels are proteins that regulate the flow of ions across cell membranes, playing a vital role in cervical cancer development and progression. These channels serve as both potential diagnostic markers and therapeutic targets, offering new opportunities for cancer treatment. Moreover, ion channels [...] Read more.
Ion channels are proteins that regulate the flow of ions across cell membranes, playing a vital role in cervical cancer development and progression. These channels serve as both potential diagnostic markers and therapeutic targets, offering new opportunities for cancer treatment. Moreover, ion channels are crucial molecular indicators and possible therapeutic targets due to their role in the development of cervical cancer. Our review focuses on the various types of ion channels which are associated with cervical cancer (CCa), including sodium, calcium, and potassium channels. In our review, we clarify their diagnostic and prognostic value, as well as their relationship to the prognosis and stage of the disease. We also examine how ion channels contribute to the metastasis of cervical cancer, specifically in relation to their influence on cell motility, invasion, and interaction with the tumor microenvironment. By examining preclinical and clinical research involving ion channel blockers and modulators, we also highlight the therapeutic potential of targeting ion channels. We have demonstrated the available assays and imaging methods based on ion channel activity as examples of emerging diagnostic breakthroughs that show promise for enhancing the early detection of cervical cancer. Additionally, the possibility that ion channel modulator-based combination therapy could improve the efficacy of traditional treatments is investigated. To demonstrate the potential of ion channels in cervical cancer diagnosis and treatment, our review highlights the current challenges and the promising role in cervical cancer diagnostics and therapy. Full article
(This article belongs to the Collection Ion Channels in Cancer Therapies)
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16 pages, 2439 KiB  
Article
SIRT1 Mediates the Effects of Sera from Athletes Who Engage in Aerobic Exercise Training in Activating Cells for Wound Healing
by Raffaella Belvedere, Nunzia Novizio, Berenice Stefanelli, Carmine Sellitto, Mariangela Palazzo, Marta Trucillo, Antonio De Luca, Emanuela De Bellis, Graziamaria Corbi, Amelia Filippelli, Valeria Conti and Antonello Petrella
Biomedicines 2025, 13(5), 1041; https://doi.org/10.3390/biomedicines13051041 - 25 Apr 2025
Viewed by 477
Abstract
Background/Objectives: Exercise training (ET) can improve wound healing and prevent the recurrence of skin lesions. Aerobic ET stimulates the NAD+-dependent deacetylase sirtuin 1 (SIRT1). The beneficial effects of ET and SIRT1 activation in wound healing have been characterized when considered separately. This study [...] Read more.
Background/Objectives: Exercise training (ET) can improve wound healing and prevent the recurrence of skin lesions. Aerobic ET stimulates the NAD+-dependent deacetylase sirtuin 1 (SIRT1). The beneficial effects of ET and SIRT1 activation in wound healing have been characterized when considered separately. This study aimed to investigate the potential role of SIRT1 as a mediator of the effects of sera isolated from athletes who regularly participate in aerobic ET (middle-distance running, MDR) on cells primarily involved in wound healing. Methods: Human keratinocytes, fibroblasts and endothelial cells were conditioned with sera from middle-distance runners and age-matched sedentary subjects (sed). Cell motility, angiogenesis and the expression of key biomarkers of cell activation were evaluated in the presence or absence of the selective SIRT1 inhibitor EX-527. Results: Higher SIRT1 activity was detected in all of the cell lines conditioned with the MDR group sera compared with that in the cells in the sed group sera. The involvement of SIRT1 was demonstrated by EX-527’s selective inhibition. Alongside the increase in SIRT1 activity, a marked increase in migration, invasion and angiogenesis was observed. The levels of E-cadherin decreased while those of integrin β1 and vinculin increased in the keratinocytes and fibroblasts conditioned with the MDR group sera compared to these values with the sed group sera, respectively. Increased levels of differentiation markers, such as involucrin in the keratinocytes, FAP1α in the fibroblasts and CD31 in the endothelial cells, were observed with the MDR group sera compared to these values using the sed group sera. Conclusions: The ex vivo/in vitro approach used here links aerobic ET-induced SIRT1 activity to proper tissue regeneration. Full article
(This article belongs to the Special Issue Wound Healing: From Basic to Clinical Research)
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