ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway

Wang, Tingjun; Wang, Gang; Shan, Danni; Fang, Yayun; Zhou, Fenfang; Yu, Mengxue; Ju, Lingao; Li, Gang; Xiang, Wan; Qian, Kaiyu; Zhang, Yi; Xiao, Yu; Wang, Xinghuan

doi:10.7150/jca.95549

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J Cancer 2024; 15(11):3297-3312. doi:10.7150/jca.95549 This issue Cite

Research Paper

ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway

Tingjun Wang^1,#, Gang Wang^1,2,#, Danni Shan^2,#, Yayun Fang², Fenfang Zhou³, Mengxue Yu², Lingao Ju², Gang Li², Wan Xiang², Kaiyu Qian^1,2, Yi Zhang^4,5, Yu Xiao^2,✉, Xinghuan Wang^1,6,✉

1. Department of Urology, Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
2. Department of Biological Repositories, Human Genetic Resources Preservation Center of Hubei Province, Hubei Key Laboratory of Urological Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China.
3. Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, China.
4. Euler Technology, ZGC Life Sciences Park, Beijing, China.
5. Center for Quantitative Biology, School of Life Sciences, Peking University, Beijing, China.
6. Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.
^#These authors contributed equally to this work.

Citation:

Wang T, Wang G, Shan D, Fang Y, Zhou F, Yu M, Ju L, Li G, Xiang W, Qian K, Zhang Y, Xiao Y, Wang X. ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway. J Cancer 2024; 15(11):3297-3312. doi:10.7150/jca.95549. https://www.jcancer.org/v15p3297.htm

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Abstract

Acetyl-CoA acetyltransferase 1 (ACAT1) plays a significant role in the regulation of gene expression and tumorigenesis. However, the biological role of ACAT1 in bladder cancer (BLCA) has yet to be elucidated. This research aimed to elucidate the bioinformatics features and biological functions of ACAT1 in BLCA. Here, we demonstrate that ACAT1 is elevated in BLCA tissues and is correlated with specific clinicopathological features and an unfavorable prognosis for survival in BLCA patients. ACAT1 was identified as an independent risk factor in BLCA. Phenotypically, both in vitro and in vivo, ACAT1 knockdown suppressed BLCA cell proliferation and migration, while ACAT1 overexpression had the opposite effect. Mechanistic assays revealed that ACAT1 enhances BLCA cell proliferation and metastasis through the AKT/GSK3β/c-Myc signaling pathway by modulating the cell cycle and EMT. Taken together, the results of our study reveal that ACAT1 is an oncogenic driver in BLCA that enhances tumor proliferation and metastasis, indicating its potential as a diagnostic and therapeutic target for this disease.

Keywords: bladder cancer, ACAT1, AKT/GSK3β/c-Myc, proliferation, metastasis

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APA

Wang, T., Wang, G., Shan, D., Fang, Y., Zhou, F., Yu, M., Ju, L., Li, G., Xiang, W., Qian, K., Zhang, Y., Xiao, Y., Wang, X. (2024). ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway. Journal of Cancer, 15(11), 3297-3312. https://doi.org/10.7150/jca.95549.

ACS

Wang, T.; Wang, G.; Shan, D.; Fang, Y.; Zhou, F.; Yu, M.; Ju, L.; Li, G.; Xiang, W.; Qian, K.; Zhang, Y.; Xiao, Y.; Wang, X. ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway. J. Cancer 2024, 15 (11), 3297-3312. DOI: 10.7150/jca.95549.

NLM

CSE

Wang T, Wang G, Shan D, Fang Y, Zhou F, Yu M, Ju L, Li G, Xiang W, Qian K, Zhang Y, Xiao Y, Wang X. 2024. ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway. J Cancer. 15(11):3297-3312.

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