Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia.

ABSTRACT: Notch regulates cell-cell contact-dependent signaling and is activated by hypoxia, a microenvironmental condition that promotes cellular invasion during both normal physiology and disease. The mechanisms by which hypoxia and Notch regulate cellular invasion are not fully elucidated. In this paper, we show that, in cancer cells, hypoxia increased the levels and activity of the ADAM12 metalloprotease in a Notch signaling-dependent manner, leading to increased ectodomain shedding of the epidermal growth factor (EGF) receptor (EGFR) ligand heparin-binding EGF-like growth factor. Released HB-EGF induced the formation of invadopodia, cellular structures that aid cancer cell invasion. Thus, we describe a signaling pathway that couples cell contact-dependent signaling with the paracrine activation

SUBMITTER: Diaz B 

PROVIDER: S-EPMC3628517 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature