The Role of the Extracellular Matrix in Cancer Stemness

Abstract

As our understanding of cancer cell biology progresses, it has become clear that tumors are a heterogenous mixture of different cell populations, some of which contain so called “cancer stem cells” (CSCs). Hallmarks of CSCs include self-renewing capability, tumor-initiating capacity and chemoresistance. The extracellular matrix (ECM), a major structural component of the tumor microenvironment, is a highly dynamic structure and increasing evidence suggests that ECM proteins establish a physical and biochemical niche for CSCs. In cancer, abnormal ECM dynamics occur due to disrupted balance between ECM synthesis and secretion and altered expression of matrix-remodeling enzymes. Tumor-derived ECM is biochemically distinct in its composition and is stiffer compared to normal ECM. In this review, we will provide a brief overview of how different components of the ECM modulate CSC properties then discuss how physical, mechanical, and biochemical cues from the ECM drive cancer stemness. Given the fact that current CSC targeting therapies face many challenges, a better understanding of CSC-ECM interactions will be crucial to identify more effective therapeutic strategies to eliminate CSCs.

Genome-Wide Identification and Characterization of DNA Methylation and Long Non-Coding RNA Expression in Gastric Cancer

“…GSEA results revealed that RP5-881L22.5 was likely to be involved in an extracellular matrix (ECM) interaction pathway. Glycoproteins make the ECM a cohesive network of molecules by linking cells together with structural components (Nallanthighal et al, 2019). Adhesive glycoproteins can bind to ECM components to activate downstream signaling pathways to regulate epithelial-mesenchymal transition, selfrenewal, migration, differentiation, and proliferation (Naba et al, 2016;Song et al, 2017).…”

Identification of genes associated with cancer stem cell characteristics in head and neck squamous cell carcinoma through co‐expression network analysis

“…26 Several studies have showed that ECM can serve as a niche for CSCs, providing structural and biochemical support to regulate proliferation, selfrenewal and differentiation of CSCs. 27 ECM stiffness as a physical properties of the ECM played a crucial role in regulating self-renewal and differentiation of CSCs through the formation of focal adhesions and subsequent activation of mechanotransduction pathways such as PI3K-AKT, Rho/ROCK, YAP/TAZ signaling pathway. [28][29][30] The above also confirmed our KEGG pathway enrichment analysis results.…”

Therapy Resistance, Cancer Stem Cells and ECM in Cancer: The Matrix Reloaded

“…Additionally, it is well established that the CSCs can reside in niches within the microenvironment [ 15 ] Moreover, the ECM niche provides structural support to the tissue and widely influences cell behavior [ 16 ]. The impact on the functional properties of CSCs is mediated by the interaction of the ECM with the cell surface receptors, specifically the integrin pathways [ 17 , 18 , 19 ].…”

“…Integrins present on the surface of tumor and stromal cells are the primary receptors involved in cell–matrix adhesion and play a profound role in the ability of the CSCs to survive in specific locations. However, in some cases, these receptors can also function in the absence of ligand binding to promote stemness and survival in the presence of environmental and therapeutic stresses [ 19 ].…”