発がんと突然変異誘発のジャーナル

概要

A Rare Bird among Major Extracellular Matrix Proteins: EMILIN1 and the Tumor Suppressor Function

Eliana Pivetta, Alfonso Colombatti and Paola Spessotto

Extracellular Matrix (ECM) proteins constitute a complex network of macromolecules with distinctive physical, biochemical, and biomechanical properties. They are expressed dynamically and their cellular functions are highly dependent upon cues from the local environment. ECM proteins primarily by interaction with integrins on the cell surface initiate downstream signaling events that involve diverse cellular functions. Although tightly controlled under normal development, the ECM is commonly deregulated and becomes disorganized in diseases such as cancer. Abnormal ECM affects cancer progression by directly promoting cellular transformation, metastasis and facilitates tumor-associated angiogenesis and inflammation, and thus leads to generation of a tumorigenic microenvironment. In this review, we summarize and discuss the current knowledge of the diverse promoting or inhibiting role played by selected members (collagen, fibronectin, tenascin, thrombospondin, LTBP-2, fibulin, CCN1, decorin, EMILIN2) of the ECM play within the microenvironment that influences tumor progression with an emphasis on EMILIN1. This glycoprotein, a member of the gC1q domain superfamily, is involved in the maintenance of the blood pressure, the proper function of lymphatic capillaries and collecting vessels and, via the interaction with the α4β1 and/or the α9β1 integrins, regulates cell proliferation. This last function highlights the peculiar role of EMILIN1 as an anti-proliferative member of the ECM and likely a novel tumor suppressor.