PGE2 mediates EGFR internalization and nuclear translocation via caveolin endocytosis promoting its transcriptional activity and proliferation in human NSCLC cells.

ABSTRACT: Prostaglandin E₂ (PGE₂) contributes to tumor progression by promoting cancer cell growth, invasion and by creating a favorable pro-tumor microenvironment. PGE₂ has been reported to transactivate and internalize into the nucleus receptor tyrosine kinases such as Epidermal growth factor receptor (EGFR), thereby supporting tumor progression. Here we demonstrate that in non-small cell lung carcinoma (NSCLC) cells, PGE₂ induces EGFR nuclear translocation via different dynamin-dependent endocytic pathways, promotes the formation of an EGFR-STAT3 complex, affects nuclear EGFR target gene expression and mediates tumor cell proliferation. Indeed, we find that PGE₂ induces EGFR internalization and consequent nuclear import through Clathrin- and

SUBMITTER: Bazzani L 

PROVIDER: S-EPMC5871088 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature