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ARHGAP6 inhibits bladder cancer cell viability, migration, and invasion via β-catenin signaling and enhances mitomycin C sensitivity

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Abstract

The Rho/ROCK pathway regulates diverse cellular processes and contributes to the development and advancement of several types of human cancers. This study investigated the role of specific Rho GTPase-activating proteins (RhoGAP), ARHGAP6, in bladder cancer (BC). In this study, ARHGAP6 expression in BC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor‐related function and the underlying molecular mechanism ARHGAP6 of in BC. The mRNA and protein levels of ARHGAP6 significantly reduced in human BC tissues and cell lines compared with corresponding adjacent non-cancerous tissues and normal urothelial cells. In vitro, ARHGAP6 overexpression markedly decreased the viability, migration, and invasion of BC cells. Interestingly, low ARHGAP6 expression in BC strongly correlated with poor patient survival and was highly associated with metastasis and β-catenin signaling. Furthermore, ARHGAP6 expression strongly influenced the sensitivity of BC cells to mitomycin C treatment. Together, our results demonstrate that ARHGAP6 plays critical roles in regulating the proliferation, migration, invasion, and metastasis of BC cells possibly via the modulation of β-catenin and strongly influences the chemosensitivity of BC cells.

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Funding

This research was funded by the National Natural Science Foundation of China (81774064), Shanghai Pujiang Program (18PJD042), and the Foundation of Pudong New District’s Medical Discipline Priority (PWZzk2022-22).

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Author notes

  1. Weihua Chen, Mingyue Tan, and Chao Yu contributed equally to this article.

Authors and Affiliations

  1. Department of Urology, Shanghai East Hospital, Tongji University, Shanghai, 200120, China

    Weihua Chen

  2. Department of Urology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200021, Shanghai, China

    Mingyue Tan

  3. Department of Urology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China

    Chao Yu & Jie Bai

  4. Department of Urology, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, No. 1500 Zhouyuan Road, Pudong, 201318, Shanghai, China

    Guoqiang Liao, Bo Yang & Hua Gong

  5. Department of Radiology, Stanford University School of Medicine, Stanford, CA, 94305, USA

    Dehui Kong

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  1. Weihua Chen
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Correspondence to Bo Yang or Hua Gong.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This usage of clinical samples was reviewed and approved by the Ethical Board at Longhua Hospital, Shanghai University of Traditional Chinese Medicine with written informed consent from all the patients. All animal experiments involved in this study were approved by the Ethics Committee of Longhua Hospital, Shanghai University of Traditional Chinese Medicine. All methods were carried out in accordance with relevant guidelines and regulations. The study is reported in accordance with the ARRIVE guidelines. The approval number of the clinical study and that of the animal study is 22017LCSY337.

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Chen, W., Tan, M., Yu, C. et al. ARHGAP6 inhibits bladder cancer cell viability, migration, and invasion via β-catenin signaling and enhances mitomycin C sensitivity. Human Cell 36, 786–797 (2023). https://doi.org/10.1007/s13577-023-00860-3

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