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.
Background:
Prostate cancer (PCa) is a common malignant tumor in males, and castration-resistant prostate cancer (CRPC) represents an advanced stage with limited treatment options and poor prognosis. Talin-1 (TLN1) is a cytoskeletal protein implicated in tumor progression, but its specific role and mechanism in CRPC remain unclear.
Methods:
Mass spectrometry (MS) was used to analyze serum peptides from patients with hormone-sensitive prostate cancer (HSPC) and CRPC. TLN1 expression was further validated in clinical prostate tissue samples (59 PCa, 17 benign prostatic hyperplasia) via immunohistochemistry, qPCR, and Western blot. Functional assays (CCK-8, colony formation, wound healing, Transwell) and a nude mouse xenograft model were employed to assess the effects of TLN1 knockdown on CRPC cell lines (DU145, PC3). Transcriptome sequencing, molecular docking, and co-immunoprecipitation (Co-IP) were conducted to explore downstream mechanisms and interactions. Western blot analysis was applied to examine the impact of TLN1 knockdown on apoptosis and the PI3K-AKT, MAPK, and NF-κB signaling pathways in CRPC cell lines. Rescue experiments were performed by knocking down both TLN1 and nerve growth factor receptor (NGFR).
Results:
TLN1 expression was significantly upregulated in CRPC patient serum and PCa tissues. Knockdown of TLN1 inhibited proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), promoted apoptosis in CRPC cells, and suppressed tumor growth in vivo. Transcriptome analysis identified NGFR as significantly upregulated upon TLN1 knockdown. TLN1 knockdown can influence the malignant progression of CRPC through the MAPK and PI3K-AKT signaling pathways. Molecular docking and Co-IP confirmed a direct interaction between TLN1 and NGFR. Knockdown of NGFR reversed the tumor-suppressive effects induced by TLN1 silencing.
Conclusions:
TLN1 inhibits the progression of CRPC by interacting with and regulating the tumor suppressor NGFR. The TLN1/NGFR axis represents a novel potential therapeutic target for CRPC.
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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