Extracellular Matrix Proteins in Cancer (2nd Edition)

Dear Colleagues,

Building upon the success of our previous Special Issue, “Extracellular Matrix Proteins in Cancer” (https://www.mdpi.com/journal/cancers/special_issues/34J8049I68), we are pleased to announce the second edition, which will further explore the critical role of the extracellular matrix (ECM) in cancer.

The extracellular matrix (ECM) is no longer considered a passive scaffold for tissue architecture but rather a dynamic and bioactive component of the tumor microenvironment (TME). Comprising a diverse array of proteins such as collagens, proteoglycans, glycoproteins, glycosaminoglycans, and matricellular regulators, the ECM actively orchestrates cellular functions including proliferation, migration adhesion, autophagy, and apoptosis through biochemical and biomechanical cues. In cancer, the profound remodeling of the ECM drives tumor progression, invasion, metastasis, and therapy resistance.

The TME is shaped by complex interactions between malignant cells, stromal fibroblasts, endothelial cells, immune infiltrates, and the ECM. Stromal cells, particularly cancer-associated fibroblasts (CAFs), deposit and reorganize ECM proteins, leading to aberrant matrix stiffening, fiber alignment, and increased crosslinking. These structural alterations elevate interstitial fluid pressure, impair drug penetration, and establish a mechanical niche that favors malignant growth. At the molecular level, mechanotransduction pathways—activated through integrins, focal adhesions, and mechanosensitive ion channels—translate ECM-derived mechanical forces into intracellular signals that sustain oncogenic pathways and alter the fate of cells.

ECM stiffening and altered viscoelasticity not only promote epithelial-to-mesenchymal transition (EMT) and invasive phenotypes but also influence angiogenesis and immune evasion by modulating the bioavailability of growth factors and cytokines. The proteolytic degradation of ECM proteins further reshapes the TME, releasing stored growth factors and generating bioactive fragments (matrikines) that regulate tumor cell migration and stromal activation. The resulting reciprocal crosstalk between ECM dynamics, stromal cells, and tumor cells underscores the central role of the ECM in defining cancer biology.

In this Special Issue, we will highlight the multifaceted roles of ECM proteins in cancer, emphasizing their contributions to mechanotransduction, stromal remodeling, matrix stiffening, and the establishment of interstitial pressure. Understanding how these processes converge to regulate tumor progression offers not only mechanistic insights but also new therapeutic opportunities, as targeting ECM components and their signaling networks holds promise in improving cancer treatment. Potential subtopics include, but are not limited to, the following:

• ECM-remodeling enzymes and their inhibitors in cancer progression;
• The role of ECM in cancer stem cell maintenance and drug resistance;
• ECM-mediated mechanotransduction and signaling pathways in tumors;
• Interactions between ECM components and immune cells in the tumor microenvironment;
• Novel therapeutic strategies targeting the ECM in cancer.

We welcome the submission of original research articles and reviews that will advance our understanding of these and related themes.

We look forward to receiving your valuable contributions.

Dr. Dragana Nikitovic
Dr. Aikaterini Berdiaki
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 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. Cancers 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 2900 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.

• extracellular matrix (ECM)
• tumor microenvironment (TME)
• stromal remodeling
• cancer-associated fibroblasts (CAFs)
• fibrous proteins
• mechanotransduction
• interstitial fluid pressure
• proteoglycans and glycoproteins
• matrix crosslinking
• epithelial-to-mesenchymal transition (EMT)
• angiogenesis
• matrikines
• therapy resistance