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TNIK drives castration-resistant prostate cancer via phosphorylating EGFR

2023; Cell Press; Volume: 27; Issue: 1 Linguagem: Inglês

10.1016/j.isci.2023.108713

2589-0042

Jianing Guo, Jiaming Liang, Youzhi Wang, Tao Guo, Yihao Liao, Boqiang Zhong, Shuyue Guo, Qian Cao, Junbo Li, Amilcar Flores‐Morales, Yuanjie Niu, Ning Jiang,

Prostate Cancer Treatment and Research

The development of castration-resistant prostate cancer (CRPC) is driven by intricate genetic and epigenetic mechanisms. Traf2- and Nck-interacting kinase (TNIK) has been reported as a serine/threonine kinase associated with tumor cell proliferation or unfavorable cancer behavior. The microarray approach revealed a substantial upregulation of TNIK expression levels, enabling us to investigate the functional behaviors of the TNIK gene in CRPC. Specifically, we discovered that AR suppresses TNIK gene transcription in LNCaP and C4-2 cells by forming a complex with H3K27me3. Following the reduction of AR levels induced by androgen deprivation therapy (ADT), TNIK is recruited to activate EGFR signaling through phosphorylation in C4-2 cells, thereby promoting CRPC progression. Our findings unveil a regulatory role of AR as a repressor for TNIK while also highlighting how TNIK activates the EGFR pathway via phosphorylation to drive CRPC progression. Consequently, targeting TNIK may represent an appealing therapeutic strategy for CRPC.