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Advances in Proteomics in Cancer

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 June 2025 | Viewed by 8943

Special Issue Editor


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Guest Editor
Laboratory of Applied Toxinology, Center of Toxins, Immune-Response and Cell Signaling LETA/CeTICS, Butantan Institute, São Paulo, Brazil
Interests: mass spectrometry-based proteomics; cancer; snake venom; scorpion venom; envenomation
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Special Issue Information

Dear Colleagues,

Proteomics studies have become an important technique applied to cancer research by providing information on protein identity, expression levels, and the description of post-translational modifications. This information plays a significant role in identifying biomarkers and therapeutic targets, and it may help to unravel key information on tumor growth and metastasis. Therefore, proteomics is crucial in the generation of datasets of potential diagnostic, prognostic, and therapeutic significance in human cancer.

Additionally, the integration of proteomics studies with other omics has provided extensive data on molecular mechanisms and target modulators. These data can be analyzed using bioinformatic pipelines to obtain useful information.

This Special Issue aims to highlight recent cutting-edge research in proteomic techniques applied to cancer research.

Dr. Leo Kei Iwai
Guest Editor

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Keywords

  • cancer
  • proteomics
  • mass spectrometry
  • molecular targets
  • biomarker

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Published Papers (6 papers)

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Research

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16 pages, 2463 KiB  
Article
Simulated Microgravity-Induced Alterations in PDAC Cells: A Potential Role for Trichostatin A in Restoring Cellular Phenotype
by Corinna Anais Pagano, Maria Angela Masini, Maurizio Sabbatini, Giorgia Gribaudo, Marcello Manfredi, Flavia Giusy Caprì, Valentina Bonetto, Valeria Magnelli, Massimo Donadelli, Roberto Corino, Masho Hilawie Belay, Elisa Robotti and Emilio Marengo
Int. J. Mol. Sci. 2025, 26(10), 4758; https://doi.org/10.3390/ijms26104758 - 16 May 2025
Viewed by 168
Abstract
Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic malignancies. Despite the remarkable improvement concerning treatment, late detection and resistance to clinically used chemotherapeutic agents remain major challenges. Trichostatin A (TSA), a histone deacetylase inhibitor, has been recognized as an effective therapeutic [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic malignancies. Despite the remarkable improvement concerning treatment, late detection and resistance to clinically used chemotherapeutic agents remain major challenges. Trichostatin A (TSA), a histone deacetylase inhibitor, has been recognized as an effective therapeutic agent against PDAC by inhibiting proliferation, inducing apoptosis, and sensitizing PDAC cells to chemotherapeutic agents such as gemcitabine. Microgravity has become a useful tool in cancer research due to its effects on various cellular processes. This paper presents a deep molecular and proteomic analysis investigating cell growth, the modulation of cytokeratins, and proteins related to apoptosis, cellular metabolism, and protein synthesis after TSA treatment in simulated microgravity (SMG)-exposed PaCa44 3D cells. Our analysis concerns the effects of TSA treatment on cell proliferation: the impairment of the cell cycle with the downregulation of proteins involved in Cdc42 signaling and G1/G2- and G2/M-phase transitions. Thus, we observed modification of survival pathways and proteins related to autophagy and apoptosis. We also observed changes in proteins involved in the regulation of transcription and the repair of damaged DNA. TSA treatment promotes the downregulation of some markers involved in the maintenance of the potency of stem cells, while it upregulates proteins involved in the induction and modulation of the differentiation process. Our data suggest that TSA treatment restores the cell phenotype prior to simulated microgravity exposure, and exerts an intriguing activity on PDAC cells by reducing proliferation and inducing cell death via multiple pathways. Full article
(This article belongs to the Special Issue Advances in Proteomics in Cancer)
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15 pages, 1489 KiB  
Article
Phosphoproteomics Reveals L1CAM-Associated Signaling Networks in High-Grade Serous Ovarian Carcinoma: Implications for Radioresistance and Tumorigenesis
by Tihomir Zh Todorov, Ricardo Coelho, Francis Jacob, Viola Heinzelmann-Schwarz, Roger Schibli, Martin Béhé, Jürgen Grünberg and Michal Grzmil
Int. J. Mol. Sci. 2025, 26(10), 4585; https://doi.org/10.3390/ijms26104585 - 10 May 2025
Viewed by 435
Abstract
Quantitative phosphoproteomics enables the comprehensive analysis of signaling pathways driven by overexpressed cancer receptors, revealing the molecular mechanisms that underpin tumor progression and therapy resistance. The glycoprotein L1 cell adhesion molecule (L1CAM) is overexpressed in high-grade serous ovarian carcinoma (HGSOC) and plays a [...] Read more.
Quantitative phosphoproteomics enables the comprehensive analysis of signaling pathways driven by overexpressed cancer receptors, revealing the molecular mechanisms that underpin tumor progression and therapy resistance. The glycoprotein L1 cell adhesion molecule (L1CAM) is overexpressed in high-grade serous ovarian carcinoma (HGSOC) and plays a crucial role in carcinogenesis by regulating cancer stem cell properties. Here, CRISPR–Cas9-mediated knockout of L1CAM in ovarian cancer OVCAR8 and OVCAR4 cells significantly impaired anchor-independent growth in soft agar assays and reduced clonogenic survival following external beam irradiation. In vivo, L1CAM knockout decreased cancer stem cell frequency and significantly decreased tumorigenicity. To uncover L1CAM-regulated signaling networks, we employed quantitative phosphoproteomics and proteomics. Bioinformatics analyses and validation studies revealed L1CAM-associated pathways that contribute to radioresistance through DNA repair processes and mammalian target or rapamycin complex 1 (mTORC1)-mediated signaling. In conclusion, our study established a link between L1CAM-dependent tumorigenesis and radioresistance, both hallmarks of cancer stemness, with phosphorylation of key proteins involved in DNA damage response. This study further emphasizes the value of quantitative phosphoproteomics in cancer research, showcasing its ability to enhance understanding of cancer progression and therapy resistance. Full article
(This article belongs to the Special Issue Advances in Proteomics in Cancer)
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22 pages, 3193 KiB  
Article
Crucial Parameters for Immunopeptidome Characterization: A Systematic Evaluation
by Pablo Juanes-Velasco, Carlota Arias-Hidalgo, Marina L. García-Vaquero, Janet Sotolongo-Ravelo, Teresa Paíno, Quentin Lécrevisse, Alicia Landeira-Viñuela, Rafael Góngora, Ángela-Patricia Hernández and Manuel Fuentes
Int. J. Mol. Sci. 2024, 25(17), 9564; https://doi.org/10.3390/ijms25179564 - 3 Sep 2024
Viewed by 2309
Abstract
Immunopeptidomics is the area of knowledge focused on the study of peptides assembled in the major histocompatibility complex (MHC), or human leukocyte antigen (HLA) in humans, which could activate the immune response via specific and selective T cell recognition. Advances in high-sensitivity mass [...] Read more.
Immunopeptidomics is the area of knowledge focused on the study of peptides assembled in the major histocompatibility complex (MHC), or human leukocyte antigen (HLA) in humans, which could activate the immune response via specific and selective T cell recognition. Advances in high-sensitivity mass spectrometry have enabled the detailed identification and quantification of the immunopeptidome, significantly impacting fields like oncology, infections, and autoimmune diseases. Current immunopeptidomics approaches primarily focus on workflows to identify immunopeptides from HLA molecules, requiring the isolation of the HLA from relevant cells or tissues. Common critical steps in these workflows, such as cell lysis, HLA immunoenrichment, and peptide isolation, significantly influence outcomes. A systematic evaluation of these steps led to the creation of an ‘Immunopeptidome Score’ to enhance the reproducibility and robustness of these workflows. This score, derived from LC-MS/MS datasets (ProteomeXchange identifier PXD038165), in combination with available information from public databases, aids in optimizing the immunopeptidome characterization process. The ‘Immunopeptidome Score’ has been applied in a systematic analysis of protein extraction, HLA immunoprecipitation, and peptide recovery yields across several tumor cell lines enabling the selection of peptides with optimal features and, therefore, the identification of potential biomarker and therapeutic targets. Full article
(This article belongs to the Special Issue Advances in Proteomics in Cancer)
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23 pages, 6669 KiB  
Article
Multi-Omics Characterization of E3 Regulatory Patterns in Different Cancer Types
by Zhongyan Li, Jingting Wan, Shangfu Li, Yun Tang, Yang-Chi-Dung Lin, Jie Ni, Xiaoxuan Cai, Jinhan Yu, Hsien-Da Huang and Tzong-Yi Lee
Int. J. Mol. Sci. 2024, 25(14), 7639; https://doi.org/10.3390/ijms25147639 - 11 Jul 2024
Viewed by 1751
Abstract
Ubiquitination, a post-translational modification, refers to the covalent attachment of ubiquitin molecules to substrates. This modification plays a critical role in diverse cellular processes such as protein degradation. The specificity of ubiquitination for substrates is regulated by E3 ubiquitin ligases. Dysregulation of ubiquitination [...] Read more.
Ubiquitination, a post-translational modification, refers to the covalent attachment of ubiquitin molecules to substrates. This modification plays a critical role in diverse cellular processes such as protein degradation. The specificity of ubiquitination for substrates is regulated by E3 ubiquitin ligases. Dysregulation of ubiquitination has been associated with numerous diseases, including cancers. In our study, we first investigated the protein expression patterns of E3 ligases across 12 cancer types. Our findings indicated that E3 ligases tend to be up-regulated and exhibit reduced tissue specificity in tumors. Moreover, the correlation of protein expression between E3 ligases and substrates demonstrated significant changes in cancers, suggesting that E3-substrate specificity alters in tumors compared to normal tissues. By integrating transcriptome, proteome, and ubiquitylome data, we further characterized the E3-substrate regulatory patterns in lung squamous cell carcinoma. Our analysis revealed that the upregulation of the SKP2 E3 ligase leads to excessive degradation of BRCA2, potentially promoting tumor cell proliferation and metastasis. Furthermore, the upregulation of E3 ubiquitin–protein ligase TRIM33 was identified as a biomarker associated with a favorable prognosis by inhibiting the cell cycle. This work exemplifies how leveraging multi-omics data to analyze E3 ligases across various cancers can unveil prognosis biomarkers and facilitate the identification of potential drug targets for cancer therapy. Full article
(This article belongs to the Special Issue Advances in Proteomics in Cancer)
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14 pages, 2212 KiB  
Article
Peptosome: A New Efficient Transfection Tool as an Alternative to Liposome
by Maliheh Manteghi, Ozge Can and Tanil Kocagoz
Int. J. Mol. Sci. 2024, 25(13), 6918; https://doi.org/10.3390/ijms25136918 - 24 Jun 2024
Viewed by 1658
Abstract
Gene therapy is one of the most promising techniques for treating genetic diseases and cancer. The current most important problem in gene therapy is gene delivery. Viral and non-viral vectors like liposomes, used for gene delivery, have many limitations. We have developed new [...] Read more.
Gene therapy is one of the most promising techniques for treating genetic diseases and cancer. The current most important problem in gene therapy is gene delivery. Viral and non-viral vectors like liposomes, used for gene delivery, have many limitations. We have developed new hybrid peptides by combining cell-penetrating peptides (CPPs) with the DNA-binding domain of the human histone H4 protein. These small peptides bind to DNA molecules through their histone domain, leaving the CPP part free and available for binding and penetration into cells, forming complexes that we named “peptosomes”. We evaluated the transfection efficiency of several hybrid peptides by delivering a plasmid carrying the green fluorescent protein gene and following its expression by fluorescent microscopy. Among several hybrid peptides, TM3 achieved a gene delivery efficiency of 76%, compared to 52% for Lipofectamine 2000. TM3 peptosomes may become important gene delivery tools with several advantages over current gene delivery agents. Full article
(This article belongs to the Special Issue Advances in Proteomics in Cancer)
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Review

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18 pages, 4360 KiB  
Review
Proteomic Investigation of Immune Checkpoints and Some of Their Inhibitors
by Marco Agostini, Pietro Traldi and Mahmoud Hamdan
Int. J. Mol. Sci. 2024, 25(17), 9276; https://doi.org/10.3390/ijms25179276 - 27 Aug 2024
Viewed by 1440
Abstract
Immune checkpoints are crucial molecules for the maintenance of antitumor immune responses. The activation or inhibition of these molecules is dependent on the interactions between receptors and ligands; such interactions can provide inhibitory or stimulatory signals to the various components of the immune [...] Read more.
Immune checkpoints are crucial molecules for the maintenance of antitumor immune responses. The activation or inhibition of these molecules is dependent on the interactions between receptors and ligands; such interactions can provide inhibitory or stimulatory signals to the various components of the immune system. Over the last 10 years, the inhibition of immune checkpoints, such as cytotoxic T lymphocyte antigen-4, programmed cell death-1, and programmed cell death ligand-1, has taken a leading role in immune therapy. This relatively recent therapy regime is based on the use of checkpoint inhibitors, which enhance the immune response towards various forms of cancer. For a subset of patients with specific forms of cancer, these inhibitors can induce a durable response to therapy; however, the medium response rate to such therapy remains relatively poor. Recent research activities have demonstrated that the disease response to this highly promising therapy resembles the response of many forms of cancer to chemotherapy, where an encouraging initial response is followed by acquired resistance to treatment and progress of the disease. That said, these inhibitors are now used as single agents or in combination with chemotherapies as first or second lines of treatment for about 50 types of cancer. The prevailing opinion regarding immune therapy suggests that for this approach of therapy to deliver on its promise, a number of challenges have to be circumvented. These challenges include understanding the resistance mechanisms to immune checkpoint blockade, the identification of more efficient inhibitors, extending their therapeutic benefits to a wider audience of cancer patients, better management of immune-related adverse side effects, and, more urgently the identification of biomarkers, which would help treating oncologists in the identification of patients who are likely to respond positively to the immune therapies and, last but not least, the prices of therapy which can be afforded by the highest number of patients. Numerous studies have demonstrated that understanding the interaction between these checkpoints and the immune system is essential for the development of efficient checkpoint inhibitors and improved immune therapies. In the present text, we discuss some of these checkpoints, their inhibitors, and some works in which mass spectrometry-based proteomic analyses were applied. Full article
(This article belongs to the Special Issue Advances in Proteomics in Cancer)
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