Osteopontin-integrin engagement induces HIF-1α-TCF12-mediated endothelial-mesenchymal transition to exacerbate colorectal cancer.

ABSTRACT: Osteopontin (OPN) is a multi-functional phospho-glycoprotein that can stimulate angiogenesis through acting on endothelial cells. As angiogenic sprouting involves endothelial-to-mesenchymal transition (EndoMT), we are intrigued to know whether OPN exerts an effect on EndoMT. Clinically, we indeed detected EndoMT-derived cells next to OPN-expressing cells in colorectal cancer tissues. Furthermore, we treated OPN to primary cultures of endothelial cells to investigate the EndoMT-inducing activity and the underlying mechanisms. Integrin α_Vβ₃ rather than CD44 is involved in OPN-induced EndoMT. OPN-integrin α_Vβ₃ engagement induces HIF-1α expression through a PI3K/Akt/TSC2-mediated and mTORC1-dependent protein synthesis pathway, which in turn trans-act

SUBMITTER: Fan CS 

PROVIDER: S-EPMC5797029 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature