TLN1与NGFR相互作用，并通过上调NGFR抑制去势耐受性前列腺癌症的发展
TLN1 interacts with NGFR and suppresses the development of castration-resistant prostate cancer by upregulating NGFR.
摘要(中文译文)
前列腺癌（PCa）是男性常见的恶性肿瘤，而去势抵抗性前列腺癌（CRPC）是其晚期阶段，治疗选择有限且预后较差。Talin-1（TLN1）是一种与肿瘤进展相关的细胞骨架蛋白，但其在CRPC中的具体作用及机制尚不清楚。采用质谱法（MS）分析激素敏感性前列腺癌（HSPC）和CRPC患者的血清肽。通过免疫组化、qPCR和Western blot在临床前列腺组织样本（59例PCa，17例良性前列腺增生）中进一步验证TLN1的表达。采用功能实验（CCK-8、集落形成、划痕愈合、Transwell）和裸鼠异种移植模型评估TLN1敲低对CRPC细胞系（DU145、PC3）的影响。通过转录组测序、分子对接和免疫共沉淀（Co-IP）探讨下游机制及相互作用。应用Western blot分析检测TLN1敲低对CRPC细胞系凋亡及PI3K-AKT、MAPK和NF-κB信号通路的影响。通过同时敲低TLN1和神经生长因子受体（NGFR）进行挽救实验。TLN1在CRPC患者血清和PCa组织中表达显著上调。敲低TLN1可抑制CRPC细胞的增殖、迁移、侵袭和上皮-间质转化（EMT），促进凋亡，并抑制肿瘤生长。转录组分析发现，TLN1敲低后NGFR显著上调。敲低TLN1可通过MAPK和PI3K-AKT信号通路影响CRPC的恶性进展。分子对接和Co-IP证实TLN1与NGFR之间存在直接相互作用。敲低NGFR可逆转TLN1沉默诱导的肿瘤抑制作用。TLN1通过相互作用并调控抑癌因子NGFR来抑制CRPC的进展。TLN1/NGFR轴是CRPC的一个新的潜在治疗靶点。
Abstract
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. 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). 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 . 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. 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.
如何引用
AMA
Sixin Li, Anjie Chen, Chen Guo, Chenwei Gu, Zhonghao Tang, Si Shen, et al. TLN1 interacts with NGFR and suppresses the development of castration-resistant prostate cancer by upregulating NGFR.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1802129.
APA
Sixin Li, Anjie Chen, Chen Guo, Chenwei Gu, Zhonghao Tang, Si Shen, et al (2026). TLN1 interacts with NGFR and suppresses the development of castration-resistant prostate cancer by upregulating NGFR.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1802129
GB/T 7714
Sixin Li, Anjie Chen, Chen Guo, Chenwei Gu, Zhonghao Tang, Si Shen, et al. TLN1 interacts with NGFR and suppresses the development of castration-resistant prostate cancer by upregulating NGFR.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1802129.
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