Submit to Special Issue Submit Abstract to Special Issue Review for Cells Propose a Special Issue

Journal Browser

► Journal Browser

Cellular and Molecular Mechanisms of Cancer Invasion and Metastasis

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Motility and Adhesion".

Deadline for manuscript submissions: 15 September 2024 | Viewed by 8486

Share This Special Issue

Special Issue Editors

Prof. Dr. Wen G. Jiang

E-Mail Website
Guest Editor

Ground Floor, Henry Wellcome Building for Biomedical Research, University Hospital of Wales, Heath Park, Cardiff CF14 4XN, UK
Interests: cancer invasion; metastasis; angiogenesis; biomarkers; molecular profiling; novel target for metastasis
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Qingping Dou

E-Mail Website
Guest Editor

Departments of Oncology, Pharmacology, and Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA
Interests: molecular targeting; cancer prevention and therapy; drug reposition; ubiquitin–proteasome system; natural products; drug discovery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are calling for manuscripts to this Special Issue on ‘Cellular and Molecular Mechanisms of Cancer Invasion and Metastasis’ for the journal Cells. Invasion and metastasis are key hallmarks in cancer and contribute to the detrimental outcome of the patients with cancer. This Special Issue aims to collect and publish recent discoveries in this area of cancer research. Manuscripts that describe studies on the cellular and molecular mechanisms of invasion and metastasis are welcome. This may include, but is not limited to, metastasis- and invasion-related genes, signalling events underlying metastatic processes, novel markers and new targets, molecular and cellular interventions for metastasis, cell adhesion, cellular communication and junctional regulations of cancer cells, metabolic abnormalities, stromal and the microenvironment. We welcome original contributions and review articles.

We look forward to receiving your valuable contributions.

Yours sincerely,
Prof. Dr. Wen G. Jiang
Prof. Dr. Qingping Dou
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

cancer invasion
cancer metastasis
metastasis-related genes
metastasis biomarkers
novel targets
microenvironment
stromal factors

Published Papers (5 papers)

Download All Papers

Research

Jump to: Review

21 pages, 6335 KiB

Open AccessArticle

Mutant p53 Gain-of-Function Induces Migration and Invasion through Overexpression of miR-182-5p in Cancer Cells

by Tzitzijanik Madrigal, Daniel Ortega-Bernal, Luis A. Herrera, Claudia Haydée González-De la Rosa, Guadalupe Domínguez-Gómez, Elena Aréchaga-Ocampo and José Díaz-Chávez

Cells 2023, 12(20), 2506; https://doi.org/10.3390/cells12202506 - 23 Oct 2023

Viewed by 1210

Abstract

The master-key TP53 gene is a tumor suppressor that is mutated in more than 50% of human cancers. Some p53 mutants lose their tumor suppressor activity and acquire new oncogenic functions, known as a gain of function (GOF). Recent studies have shown that p53 mutants can exert oncogenic effects through specific miRNAs. We identified the differentially expressed miRNA profiles of the three most frequent p53 mutants (p53R273C, p53R248Q, and p53R175H) after their transfection into the Saos-2 cell line (null p53) as compared with p53WT transfected cells. The associations between these miRNAs and the signaling pathways in which they might participate were identified with miRPath Software V3.0. QRT-PCR was employed to validate the miRNA profiles. We observed that p53 mutants have an overall negative effect on miRNA expression. In the global expression profile of the human miRNome regulated by the p53R273C mutant, 72 miRNAs were underexpressed and 35 overexpressed; in the p53R175H miRNAs profile, our results showed the downregulation of 93 and upregulation of 10 miRNAs; and in the miRNAs expression profile regulated by the p53R248Q mutant, we found 167 decreased and 6 increased miRNAs compared with p53WT. However, we found overexpression of some miRNAs, like miR-182-5p, in association with processes such as cell migration and invasion. In addition, we explored whether the induction of cell migration and invasion by the p53R48Q mutant was dependent on miR-182-5p because we found overexpression of miR-182-5p, which is associated with processes such as cell migration and invasion. Inhibition of mutant p53R248Q and miR-182-5p increased FOXF2-MTSS1 levels and decreased cell migration and invasion. In summary, our results suggest that p53 mutants increase the expression of miR-182-5p, and this miRNA is necessary for the p53R248Q mutant to induce cell migration and invasion in a cancer cell model. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Cancer Invasion and Metastasis)

► Show Figures

Graphical abstract

19 pages, 7781 KiB

Open AccessArticle

Deciphering the Role of p60AmotL2 in Epithelial Extrusion and Cell Detachment

by Weiyingqi Cui, Aravindh Subramani, Pedro Fonseca, Yumeng Zhang, Le Tong, Yuanyuan Zhang, Lars Egevad, Andreas Lundqvist and Lars Holmgren

Cells 2023, 12(17), 2158; https://doi.org/10.3390/cells12172158 - 28 Aug 2023

Cited by 1 | Viewed by 1039

Abstract

Preserving an accurate cell count is crucial for maintaining homeostasis. Apical extrusion, a process in which redundant cells are eliminated by neighboring cells, plays a key role in this regard. Recent studies have revealed that apical extrusion can also be triggered in cells transformed by oncogenes, suggesting it may be a mechanism through which tumor cells escape their microenvironment. In previous work, we demonstrated that p60AmotL2 modulates the E-cadherin function by inhibiting its connection to radial actin filaments. This isoform of AmotL2 is expressed in invasive breast and colon tumors and promotes invasion in vitro and in vivo. Transcriptionally regulated by c-Fos, p60AmotL2 is induced by local stress signals such as severe hypoxia. In this study, we investigated the normal role of p60AmotL2 in epithelial tissues. We found that this isoform is predominantly expressed in the gut, where cells experience rapid turnover. Through time-lapse imaging, we present evidence that cells expressing p60AmotL2 are extruded by their normal neighboring cells. Based on these findings, we hypothesize that tumor cells exploit this pathway to detach from normal epithelia and invade surrounding tissues. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Cancer Invasion and Metastasis)

► Show Figures

Figure 1

24 pages, 6717 KiB

Open AccessArticle

Modulation of E-Cadherin Function through the AmotL2 Isoforms Promotes Ameboid Cell Invasion

by Aravindh Subramani, Weiyingqi Cui, Yuanyuan Zhang, Tomas Friman, Zhihai Zhao, Wenmao Huang, Pedro Fonseca, Weng-Onn Lui, Vani Narayanan, Justyna Bobrowska, Małgorzata Lekka, Jie Yan, Daniel E. Conway and Lars Holmgren

Cells 2023, 12(13), 1682; https://doi.org/10.3390/cells12131682 - 21 Jun 2023

Cited by 2 | Viewed by 1623

Abstract

The spread of tumor cells and the formation of distant metastasis remain the main causes of mortality in cancer patients. However, the mechanisms governing the release of cells from micro-environmental constraints remain unclear. E-cadherin negatively controls the invasion of epithelial cells by maintaining cell–cell contacts. Furthermore, the inactivation of E-cadherin triggers invasion in vitro. However, the role of E-cadherin is complex, as metastasizing cells maintain E-cadherin expression, which appears to have a positive role in the survival of tumor cells. In this report, we present a novel mechanism delineating how E-cadherin function is modulated to promote invasion. We have previously shown that E-cadherin is associated with p100AmotL2, which is required for radial actin formation and the transmission of mechanical force. Here, we present evidence that p60AmotL2, which is expressed in invading tumor cells, binds to the p100AmotL2 isoform and uncouples the mechanical constraint of radial actin filaments. We show for the first time that the coupling of E-cadherin to the actin cytoskeleton via p100AmotL2 is directly connected to the nuclear membrane. The expression of p60AmotL2 inactivates this connection and alters the properties of the nuclear lamina, potentiating the invasion of cells into micropores of the extracellular matrix. In summary, we propose that the balance of the two AmotL2 isoforms is important in the modulation of E-cadherin function and that an imbalance of this axis promotes ameboid cell invasion. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Cancer Invasion and Metastasis)

► Show Figures

Figure 1

22 pages, 3803 KiB

Open AccessArticle

Proteoglycan SPOCK1 as a Poor Prognostic Marker Promotes Malignant Progression of Clear Cell Renal Cell Carcinoma via Triggering the Snail/Slug-MMP-2 Axis-Mediated Epithelial-to-Mesenchymal Transition

by Yung-Wei Lin, Yu-Ching Wen, Chi-Hao Hsiao, Feng-Ru Lai, Shun-Fa Yang, Yi-Chieh Yang, Kuo-Hao Ho, Feng-Koo Hsieh, Michael Hsiao, Wei-Jiunn Lee and Ming-Hsien Chien

Cells 2023, 12(3), 352; https://doi.org/10.3390/cells12030352 - 17 Jan 2023

Cited by 2 | Viewed by 2095

Abstract

Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1) has been reported to play an oncogenic role in certain cancer types; however, the role of SPOCK1 in the progression of clear cell renal cell carcinoma (ccRCC) remains elusive. Here, higher SPOCK1 transcript and protein levels were observed in ccRCC tissues compared to normal tissues and correlated with advanced clinical stages, larger tumor sizes, and lymph node and distal metastases. Knockdown and overexpression of SPOCK1 in ccRCC cells led to decreased and increased cell clonogenic and migratory/invasive abilities in vitro as well as lower and higher tumor growth and invasion in vivo, respectively. Mechanistically, the gene set enrichment analysis (GSEA) database was used to identify the gene set of epithelial-to-mesenchymal transition (EMT) pathways enriched in ccRCC samples with high SPOCK1 expression. Further mechanistic investigations revealed that SPOCK1 triggered the Snail/Slug–matrix metalloproteinase (MMP)-2 axis to promote EMT and cell motility. Clinical ccRCC samples revealed SPOCK1 to be an independent prognostic factor for overall survival (OS), and positive correlations of SPOCK1 with MMP-2 and mesenchymal-related gene expression levels were found. We observed that patients with SPOCK1^high/MMP2^high tumors had the shortest OS times compared to others. In conclusion, our findings reveal that SPOCK1 can serve as a useful biomarker for predicting ccRCC progression and prognosis, and as a promising target for treating ccRCC. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Cancer Invasion and Metastasis)

► Show Figures

Figure 1

Review

Jump to: Research

16 pages, 951 KiB

Open AccessReview

MT1-MMP as a Key Regulator of Metastasis

by Noritaka Tanaka and Takeharu Sakamoto

Cells 2023, 12(17), 2187; https://doi.org/10.3390/cells12172187 - 31 Aug 2023

Cited by 4 | Viewed by 1601

Abstract

Membrane type1-matrix metalloproteinase (MT1-MMP) is a member of metalloproteinases that is tethered to the transmembrane. Its major function in cancer progression is to directly degrade the extracellular matrix components, which are mainly type I–III collagen or indirectly type IV collagen through the activation of MMP-2 with a cooperative function of the tissue inhibitor of metalloproteinase-2 (TIMP-2). MT1-MMP is expressed as an inactive form (zymogen) within the endoplasmic reticulum (ER) and receives truncation processing via furin for its activation. Upon the appropriate trafficking of MT1-MMP from the ER, the Golgi apparatus to the cell surface membrane, MT1-MMP exhibits proteolytic activities to the surrounding molecules such as extracellular matrix components and cell surface molecules. MT1-MMP also retains a non-proteolytic ability to activate hypoxia-inducible factor 1 alpha (HIF-1A) via factors inhibiting the HIF-1 (FIH-1)-Mint3-HIF-1 axis, resulting in the upregulation of glucose metabolism and oxygen-independent ATP production. Through various functions of MT1-MMP, cancer cells gain motility on migration/invasion, thus causing metastasis. Despite the long-time efforts spent on the development of MT1-MMP interventions, none have been accomplished yet due to the side effects caused by off-target effects. Recently, MT1-MMP-specific small molecule inhibitors or an antibody have been reported and these inhibitors could potentially be novel agents for cancer treatment. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Cancer Invasion and Metastasis)

► Show Figures