Related Experiment Video

Updated: Feb 15, 2026

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

18.7K

SEMA3C drives cancer growth by transactivating multiple receptor tyrosine kinases via Plexin B1

James W Peacock1,2, Ario Takeuchi1,3, Norihiro Hayashi1,4

  • 1Vancouver Prostate Centre, Vancouver, BC, Canada.

EMBO Molecular Medicine
|January 20, 2018
PubMed

Insights

SEMA3C promotes prostate cancer growth and treatment resistance by activating receptor tyrosine kinases (RTKs) independently of ligands. Inhibiting SEMA3C offers a new therapeutic strategy for advanced prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Growth factor receptor tyrosine kinase (RTK) pathway activation is crucial for cancer progression and treatment resistance.
  • Ligands typically stimulate RTK pathways, driving cancer cell growth and survival.

Purpose of the Study:

  • To investigate the role of SEMA3C in activating RTKs, particularly in castration-resistant prostate cancer (CRPC).
  • To explore SEMA3C inhibition as a potential therapeutic strategy for advanced prostate cancer.

Main Methods:

  • Investigated SEMA3C's interaction with Plexin B1 to activate RTKs (EGFR, ErbB2, MET) independent of cognate ligands.
  • Assessed SEMA3C expression in CRPC and its impact on cancer cell growth and resistance to androgen receptor pathway inhibitors.
  • Utilized Plexin B1 sema domain-containing:Fc fusion proteins to suppress RTK signaling and cell growth.
  • Evaluated the effect of SEMA3C inhibition on CRPC progression in LNCaP xenografts in vivo.

Main Results:

  • SEMA3C activates multiple RTKs (EGFR, ErbB2, MET) via Plexin B1 in a ligand-independent manner.
  • Increased SEMA3C expression in CRPC correlates with enhanced cancer cell growth and resistance to androgen receptor pathway inhibition.
  • SEMA3C inhibition demonstrated a delay in CRPC and enzalutamide-resistant progression.
  • Plexin B1 fusion proteins suppressed RTK signaling, reduced cell growth, and inhibited CRPC progression in vivo.

Conclusions:

  • SEMA3C is a key driver of RTK activation and progression in castration-resistant prostate cancer.
  • Targeting SEMA3C presents a promising novel therapeutic strategy for treating advanced prostate cancer and overcoming treatment resistance.
Keywords:
Plexin B1Semaphorin 3Capoptosisprostate cancerreceptor tyrosine kinase

More Related Videos

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays07:42

Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays

Published on: September 19, 2018

8.4K
Driving Under the Influence: How Music Listening Affects Driving Behaviors07:25

Driving Under the Influence: How Music Listening Affects Driving Behaviors

Published on: March 27, 2019

13.2K

Related Concept Videos

Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
19.5K
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
563
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
86.8K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.2K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

4.5K
Energy to Drive Translocation01:37

Energy to Drive Translocation

Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
2.9K