Open AccessSEMA 3C drives cancer growth by transactivating multiple receptor tyrosine kinases via Plexin B1
Author(s) -
Peacock James W,
Takeuchi Ario,
Hayashi Norihiro,
Liu Liangliang,
Tam Kevin J,
Al Nakouzi Nader,
Khazamipour Nastaran,
Tombe Tabitha,
Dejima Takashi,
Lee Kevin CK,
Shiota Masaki,
Thaper Daksh,
Lee Wilson CW,
Hui Daniel HF,
Kuruma Hidetoshi,
Ivanova Larissa,
Yenki Parvin,
Jiao Ivy ZF,
Khosravi Shahram,
Mui Alice LF,
Fazli Ladan,
Zoubeidi Amina,
Daugaard Mads,
Gleave Martin E,
Ong Christopher J
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201707689
Subject(s) - lncap , autocrine signalling , prostate cancer , cancer research , semaphorin , receptor tyrosine kinase , enzalutamide , biology , paracrine signalling , androgen receptor , plexin , tyrosine kinase , kinase , signal transduction , receptor , cancer , microbiology and biotechnology , genetics
Growth factor receptor tyrosine kinase ( RTK ) pathway activation is a key mechanism for mediating cancer growth, survival, and treatment resistance. Cognate ligands play crucial roles in autocrine or paracrine stimulation of these RTK pathways. Here, we show SEMA 3C drives activation of multiple RTK s including EGFR , ErbB2, and MET in a cognate ligand‐independent manner via Plexin B1. SEMA 3C expression levels increase in castration‐resistant prostate cancer ( CRPC ), where it functions to promote cancer cell growth and resistance to androgen receptor pathway inhibition. SEMA 3C inhibition delays CRPC and enzalutamide‐resistant progression. Plexin B1 sema domain‐containing:Fc fusion proteins suppress RTK signaling and cell growth and inhibit CRPC progression of LNC aP xenografts post‐castration in vivo . SEMA 3C inhibition represents a novel therapeutic strategy for treatment of advanced prostate cancer.