The extracellular matrix protein EMILIN1 silences the RAS-ERK pathway via ?4?1 integrin and decreases tumor cell growth.

The extracellular matrix plays a fundamental role in physiological and pathological proliferation. It exerts its function through a signal cascade starting from the integrins that take direct contact with matrix constituents most of which behave as pro-proliferative clues. On the contrary, EMILIN1, a glycoprotein interacting with the ?4?1 integrin through ...
its gC1q domain, plays a paradigmatic anti-proliferative role. Here, we demonstrate that the EMILIN1-?4 interaction de-activates the MAPK pathway through HRas. Epithelial cells expressing endogenous ?4 integrin and persistently plated on gC1q inhibited pERK1/2 increasing HRasGTP and especially the HRasGTP ubiquitinated form (HRasGTP-Ub). The drug salirasib reversed this effect. In addition, only the gC1q-ligated ?4 integrin chain co-immunoprecipitated the ubiquitinated HRas. Only epithelial cells transfected with the wild type form of the ?4 integrin chain showed the EMILIN1/?4?1/HRas/pERK1/2 link, whereas cells transfected with a ?4 integrin chain carrying a truncated cytoplasmic tail had no effect. In this study we unveiled the pathway activated by the gC1q domain of EMILIN1 through ?4?1 integrin engagement and leading to the decrease of proliferation in an epithelial system.
Mesh Terms:
Cell Adhesion, Cell Movement, Cell Proliferation, Complement C1q, Extracellular Signal-Regulated MAP Kinases, Humans, Integrin alpha4beta1, MAP Kinase Signaling System, Membrane Glycoproteins, Models, Biological, Neoplasms, Signal Transduction, ras Proteins
Oncotarget
Date: Apr. 18, 2017
Download Curated Data For This Publication
221674
Switch View:
  • Interactions 1