@article{2da800dfc3ad4351b45ea3a93eb96be8,
title = "SEMA3C drives cancer growth by transactivating multiple receptor tyrosine kinases via Plexin B1",
abstract = "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 SEMA3C drives activation of multiple RTKs including EGFR, ErbB2, and MET in a cognate ligand-independent manner via Plexin B1. SEMA3C expression levels increase in castration-resistant prostate cancer (CRPC), where it functions to promote cancer cell growth and resistance to androgen receptor pathway inhibition. SEMA3C 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 LNCaP xenografts post-castration in vivo. SEMA3C inhibition represents a novel therapeutic strategy for treatment of advanced prostate cancer.",
author = "Peacock, {James W.} and Ario Takeuchi and Norihiro Hayashi and Liangliang Liu and Tam, {Kevin J.} and {Al Nakouzi}, Nader and Nastaran Khazamipour and Tabitha Tombe and Takashi Dejima and Lee, {Kevin C.K.} and Masaki Shiota and Daksh Thaper and Lee, {Wilson C.W.} and Hui, {Daniel H.F.} and Hidetoshi Kuruma and Larissa Ivanova and Parvin Yenki and Jiao, {Ivy Z.F.} and Shahram Khosravi and Mui, {Alice L.F.} and Ladan Fazli and Amina Zoubeidi and Mads Daugaard and Gleave, {Martin E.} and Ong, {Christopher J.}",
note = "Funding Information: We would like to thank Mingshu Dong for producing the graphical abstract and cover art. This work was funded by grants from Prostate Cancer Canada (Grants # TAG2014-06 and GS2015-06), Michael Smith Foundation for Health Research (Grant # 17318), Terry Fox Foundation (Grant # TFF-116129), Canadian Cancer Society Research Institute (Grant # 700347), Cancer Research Society (Grant # F09-60564), the NIH Pacific Northwest Prostate SPORE (NCI P50 CA097186), Prostate Cancer Foundation British Columbia (Grant # F13-0016), and National Centres of Excellence of Canada (CECR PC-TRIADD). TCGA, http://cancergenome.nih.gov/. Chen et?al (), http://www.ncbi.nlm.nih.gov/geoprofiles?term=GDS535+AND+376_at. Publisher Copyright: {\textcopyright} 2018 The Authors. Published under the terms of the CC BY 4.0 license",
year = "2018",
month = feb,
doi = "10.15252/emmm.201707689",
language = "English",
volume = "10",
pages = "219--238",
journal = "EMBO Molecular Medicine",
issn = "1757-4676",
publisher = "Wiley-Blackwell",
number = "2",
}
