ERK-regulated αB-crystallin induction by matrix detachment inhibits anoikis and promotes lung metastasis in vivo.

ABSTRACT: Evasion of extracellular matrix detachment-induced apoptosis ('anoikis') is a defining characteristic of metastatic tumor cells. The ability of metastatic carcinoma cells to survive matrix detachment and escape anoikis enables them to disseminate as viable circulating tumor cells and seed distant organs. Here we report that αB-crystallin, an antiapoptotic molecular chaperone implicated in the pathogenesis of diverse poor-prognosis solid tumors, is induced by matrix detachment and confers anoikis resistance. Specifically, we demonstrate that matrix detachment downregulates extracellular signal-regulated kinase (ERK) activity and increases αB-crystallin protein and messenger RNA (mRNA) levels. Moreover, we show that ERK inhibition in adherent cancer cells mimics matrix detachment by increasi

SUBMITTER: Malin D 

PROVIDER: S-EPMC4537846 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature