Shaping Up the Tumor Microenvironment With Cellular Fibronectin

作者：Georgios Efthymiou, Angélique Saint, Michael W. Ruff, Zeinab Rekad, Delphine Ciais, Ellen Van Obberghen‐Schilling · 发表于：Frontiers in Oncology · 年份：2020 · DOI：10.3389/fonc.2020.00641 · 被引用次数：155 · 研究领域：Cell Adhesion Molecules Research、Peptidase Inhibition and Analysis、Protease and Inhibitor Mechanisms

Normal tissue homeostasis and architecture restrain tumor growth. Thus for a tumor to develop and spread, malignant cells must overcome growth-repressive inputs from surrounding tissue and escape immune surveillance mechanisms that curb cancer progression. This is achieved by promoting the conversion of a physiological microenvironment to a pro-tumoral state and it requires a constant dialog between malignant cells and ostensibly normal cells of adjacent tissue. Pro-tumoral reprogramming of the stroma is accompanied by an upregulation of certain extracellular matrix (ECM) proteins and their cognate receptors. Fibronectin (FN) is one such component of the tumor matrisome. This large multidomain glycoprotein dimer expressed over a wide range of human cancers is assembled by cell-driven forces into a fibrillar array that provides an obligate scaffold for the deposition of other matrix proteins and binding sites for functionalization by soluble factors in the tumor microenvironment. Encoded by a single gene, FN regulates the proliferation, motile behavior and fate of multiple cell types, largely through mechanisms that involve integrin-mediated signaling. These processes are coordinated by distinct isoforms of FN, collectively known as cellular FN (as opposed to circulating plasma FN) that arise through alternative splicing of the FN1 gene. Cellular FN isoforms differ in their solubility, receptor binding ability and spatiotemporal expression, and that exert functions that have y...