CD147 functions as the signaling receptor for extracellular divalent copper in hepatocellular carcinoma cells.

ABSTRACT: Elevated copper levels in tumor microenvironment are directly correlated to cancer progression in a variety of malignancies. Copper is required in angiogenesis, and promotes the proliferation and metastasis of cancer cells. However, the molecular mechanism of copper in promoting cancer progression remains elusive. Here we report that CD147 serves as a signaling receptor for extracellular Cu²⁺ in hepatocellular carcinoma (HCC) cells. Cu²⁺ binds to the extracellular membrane-proximal domain of CD147 and mediates its self-association. Cu²⁺-mediated self-association of CD147 activates PI3K/Akt signaling pathway leading to the up-regulation of matrix metalloproteinase MMP-2 and MMP-14 in HCC cells. Cu²⁺-induced CD147 self-association also enhances the

SUBMITTER: Ding P 

PROVIDER: S-EPMC5584238 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature