TLN1 interacts with NGFR and suppresses the development of castration-resistant prostate cancer by upregulating NGFR

Sixin Li1,2, Anjie Chen1,2, Chen Guo1,2

  • 1Department of Urology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.

Abstract

Insights

Talin-1 (TLN1) promotes castration-resistant prostate cancer (CRPC) progression by interacting with nerve growth factor receptor (NGFR). Targeting the TLN1/NGFR axis offers a new therapeutic strategy for CRPC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Prostate cancer (PCa) is a prevalent malignancy in males.
  • Castration-resistant prostate cancer (CRPC) signifies an advanced stage with limited therapeutic options and poor prognosis.
  • The role of Talin-1 (TLN1) in CRPC progression is not well-understood.

Purpose of the Study:

  • To investigate the role and mechanism of Talin-1 (TLN1) in castration-resistant prostate cancer (CRPC).
  • To identify potential therapeutic targets for CRPC based on TLN1's function.

Main Methods:

  • Serum peptide analysis using mass spectrometry (MS).
  • Validation of TLN1 expression in clinical samples via immunohistochemistry, qPCR, and Western blot.
  • Functional assays and in vivo xenograft models to assess TLN1 knockdown effects.
  • Transcriptome sequencing, molecular docking, and co-immunoprecipitation (Co-IP) to elucidate mechanisms and interactions.
  • Analysis of signaling pathways (PI3K-AKT, MAPK, NF-κB) and rescue experiments involving nerve growth factor receptor (NGFR).

Main Results:

  • TLN1 expression is significantly upregulated in CRPC patient serum and tissues.
  • TLN1 knockdown inhibits CRPC cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and promotes apoptosis, suppressing tumor growth in vivo.
  • TLN1 interacts directly with NGFR, and TLN1 knockdown upregulates NGFR, influencing CRPC progression via MAPK and PI3K-AKT pathways. NGFR knockdown reverses TLN1 silencing effects.

Conclusions:

  • Talin-1 (TLN1) promotes CRPC progression by interacting with and regulating the tumor suppressor nerve growth factor receptor (NGFR).
  • The TLN1/NGFR axis is identified as a novel potential therapeutic target for CRPC.

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