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.
| Original language | English |
|---|---|
| Pages (from-to) | 219-238 |
| Number of pages | 20 |
| Journal | EMBO Molecular Medicine |
| Volume | 10 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 1 2018 |
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All Science Journal Classification (ASJC) codes
- Molecular Medicine
Cite this
SEMA3C drives cancer growth by transactivating multiple receptor tyrosine kinases via Plexin B1. / Peacock, James W.; Takeuchi, Ario; Hayashi, Norihiro; Liu, Liangliang; Tam, Kevin J.; Al Nakouzi, Nader; Khazamipour, Nastaran; Tombe, Tabitha; Dejima, Takashi; Lee, Kevin C.K.; Shiota, Masaki; Thaper, Daksh; Lee, Wilson C.W.; Hui, Daniel H.F.; Kuruma, Hidetoshi; Ivanova, Larissa; Yenki, Parvin; Jiao, Ivy Z.F.; Khosravi, Shahram; Mui, Alice L.F.; Fazli, Ladan; Zoubeidi, Amina; Daugaard, Mads; Gleave, Martin E.; Ong, Christopher J.
In: EMBO Molecular Medicine, Vol. 10, No. 2, 01.02.2018, p. 219-238.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - SEMA3C drives cancer growth by transactivating multiple receptor tyrosine kinases via Plexin B1
AU - Peacock, James W.
AU - Takeuchi, Ario
AU - Hayashi, Norihiro
AU - Liu, Liangliang
AU - Tam, Kevin J.
AU - Al Nakouzi, Nader
AU - Khazamipour, Nastaran
AU - Tombe, Tabitha
AU - Dejima, Takashi
AU - Lee, Kevin C.K.
AU - Shiota, Masaki
AU - Thaper, Daksh
AU - Lee, Wilson C.W.
AU - Hui, Daniel H.F.
AU - Kuruma, Hidetoshi
AU - Ivanova, Larissa
AU - Yenki, Parvin
AU - Jiao, Ivy Z.F.
AU - Khosravi, Shahram
AU - Mui, Alice L.F.
AU - Fazli, Ladan
AU - Zoubeidi, Amina
AU - Daugaard, Mads
AU - Gleave, Martin E.
AU - Ong, Christopher J.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85040736628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040736628&partnerID=8YFLogxK
U2 - 10.15252/emmm.201707689
DO - 10.15252/emmm.201707689
M3 - Article
C2 - 29348142
AN - SCOPUS:85040736628
VL - 10
SP - 219
EP - 238
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
SN - 1757-4676
IS - 2
ER -