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Updated: Jun 21, 2025

Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
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Latrophilins as Downstream Effectors of Androgen Receptors including a Splice Variant, AR-V7, Induce Prostate Cancer

Yuki Teramoto1,2, Mohammad Amin Elahi Najafi1,2, Takuo Matsukawa1,2

  • 1Department of Pathology & Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.

International Journal of Molecular Sciences
|July 13, 2024
PubMed

Insights

Latrophilins (LPHNs) promote prostate cancer growth by acting as downstream effectors of androgen receptors (ARs). Elevated LPHN expression in tumors correlates with increased recurrence risk, highlighting their role in both AR-positive and AR-negative prostate cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • G-protein-coupled receptors

Background:

  • Latrophilins (LPHNs) are G-protein-coupled receptors, with known ligands like latrotoxin (LTX), but their role in cancer is largely unknown.
  • Prostate cancer progression involves complex molecular pathways, including androgen receptor (AR) signaling.

Purpose of the Study:

  • To investigate the role of Latrophilins (LPHN1, LPHN2, LPHN3) in the progression of prostate cancer.
  • To determine if LPHNs are regulated by androgen receptor (AR) signaling and if they influence cancer cell behavior.

Main Methods:

  • Assessed LPHN expression and function in human prostate cancer cell lines using ligand treatments (α-LTX, FLRT3) and shRNA knockdown.
  • Investigated AR binding to LPHN promoters using chromatin immunoprecipitation assays.
  • Analyzed LPHN expression in radical prostatectomy specimens via immunohistochemistry.

Main Results:

  • Dihydrotestosterone increased LPHN expression in AR-positive cells, with ARs (including AR-V7) binding to LPHN promoters.
  • Ligand treatment (α-LTX, FLRT3) enhanced cell viability and migration, and upregulated Bcl-2, p-JAK2, and p-STAT3.
  • LPHN knockdown reversed ligand-mediated effects.
  • Elevated LPHN expression in prostate cancer tissues correlated with higher recurrence risk.

Conclusions:

  • Latrophilins (LPHNs) are downstream effectors of androgen receptors (ARs) in prostate cancer.
  • LPHNs promote prostate cancer cell growth and migration, contributing to progression in androgen-sensitive, castration-resistant, and AR-negative cancers.
  • Increased LPHN expression is a potential biomarker for prostate cancer recurrence.
Keywords:
ADGRLAR-V7androgen receptorlatrophilinlatrotoxinprostate cancer

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