PLAC1 is essential for FGF7/FGFRIIIb-induced Akt-mediated cancer cell proliferation.

PLAC1 (placenta enriched 1) is a mammalian trophoblast-specific protein. Aberrant expression of PLAC1 is observed in various human cancers, where it is involved in the motility, migration, and invasion of tumor cells, which are associated with the phosphoinositide 3-kinase (PI3K)/AKT pathway. We previously demonstrated that AKT activation mediates the downstream effects of PLAC1; however, the molecular mechanisms of PLAC1-induced AKT-mediated tumor-related processes are unclear. We studied human choriocarcinoma and breast cancer cell lines to explore the localization and receptor-ligand interactions, as well as the downstream effects of PLAC1. We show secretion and adherence of PLAC1 to the extracellular matrix, where it forms a trimeric complex with fibroblast growth factor 7 (FGF7) and its receptor, FGF receptor 2 IIIb (FGFR2IIIb). We further show that PLAC1 signaling via FGFR2IIIb activates AKT phosphorylation in cancer cell lines. As the FGF pathway is of major interest in anticancer therapeutic strategies, these data further promote PLAC1 as a promising anticancer drug target.

Déclaration de conflit d'intérêts

CONFLICTS OF INTEREST OT was the founder and chief executive officer of Ganymed until the end of 2016, and is currently an employee and chief medical officer of BionTech. In addition, OT holds several patents for the investigational agent, zolbetuximab, with royalties paid to Astellas, and has also received consultancy fees from Astellas Pharma. US was the co-founder and shareholder at Ganymed and also holds several patents, with royalties paid to Astellas. He is currently the founder, chief executive officer, and shareholder of BioNTech. DBR, MG, SH-R, C Hartmann MK, hold a patent EP 2 662 386 A1 licensed to BioNTech AG, TRON gGmbH, Universitätsmedizin der Johannes Gutenberg-Universität Mainz. CR was a former employee of Ganymed. GC, TB, and SW have no conflicts of interest to disclose.