1. Academic Validation
  2. KIF26B promotes bladder cancer progression via activating Wnt/β-catenin signaling in a TRAF2-dependent pathway

KIF26B promotes bladder cancer progression via activating Wnt/β-catenin signaling in a TRAF2-dependent pathway

  • Cell Rep. 2025 May 27;44(5):115595. doi: 10.1016/j.celrep.2025.115595.
Jia-Ming Wang 1 Feng-Hao Zhang 1 Hai-Yun Xie 2 Zi-Xiang Liu 3 Yi-Jie Tang 1 Xuan Shu 1 Yu-Qing Wu 1 Ding-Heng Lu 1 Jia-Zhu Sun 1 Yu-Fan Ying 1 Xue-You Ma 1 Xiang-Yi Zheng 1 Xiao Wang 1 Ben Liu 1 Jiang-Feng Li 4 Li-Ping Xie 5 Jin-Dan Luo 6
Affiliations

Affiliations

  • 1 Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China.
  • 2 Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China.
  • 3 Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, P.R. China.
  • 4 Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China. Electronic address: lijf@zju.edu.cn.
  • 5 Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China. Electronic address: xielp@zju.edu.cn.
  • 6 Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China. Electronic address: luojindan@zju.edu.cn.
Abstract

In this study, we report that KIF26B is upregulated in bladder Cancer and acts as an independent prognostic factor. Knockdown of kif26b blocks the proliferation, metastasis, and cisplatin resistance of bladder Cancer cells. Mechanistically, TCF4 potently stimulates kif26b transcription by directly binding to its promoter. KIF26B activates the Wnt/β-catenin signaling pathway through association with TRAF2 and thus promotes the formation of the TCF4/β-catenin complex. KIF26B promotes the protein stability of TRAF2 by facilitating the OTUB2-mediated de-ubiquitination of TRAF2. Importantly, KIF26B promotes the nuclear translocation of TRAF2 through enhancing its association with IPO11, a process that is dependent on the C-terminal domain of β-catenin. Additionally, phosphorylation of tyrosine 78 in TRAF2 is essential for its binding to KIF26B in response to Wnt3a signaling. Furthermore, a KIF26B/TRAF2/PD-L1 axis is identified in bladder Cancer, and combined therapy of anti-B7-H3 antibody with kif26b knockdown yields superior anti-tumor effects.

Keywords

CP: Cancer; KIF26B; TRAF2; Wnt/β-catenin signaling; bladder cancer; pathogenesis.

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