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Int J Biol Sci 2024; 20(7):2403-2421. doi:10.7150/ijbs.87442 This issue Cite

Research Paper

Ciliogenesis-associated Kinase 1 Promotes Breast Cancer Cell Proliferation and Chemoresistance via Phosphorylating ERK1

Yanling He1#, Xinyuan Zhang1#, Weijun Pan1#, Jiebiao Zhang2#, Weiliang Zhu2, Jian Zhang2✉, Jian Shi1✉

1. Department of Pathology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, Guangdong, China.
2. Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
#Co-first authors.

✉ Corresponding authors: Jian Shi, jshiwklscom; Jian Zhang, zhangjiansmu.edu.cn.

Citation:
He Y, Zhang X, Pan W, Zhang J, Zhu W, Zhang J, Shi J. Ciliogenesis-associated Kinase 1 Promotes Breast Cancer Cell Proliferation and Chemoresistance via Phosphorylating ERK1. Int J Biol Sci 2024; 20(7):2403-2421. doi:10.7150/ijbs.87442. https://www.ijbs.com/v20p2403.htm
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Abstract

Graphic abstract

Ciliogenesis-associated kinase 1 (CILK1) plays a key role in the ciliogenesis and ciliopathies. It remains totally unclear whether CILK1 is involved in tumor progression and therapy resistance. Here, we report that the aberrant high-expression of CILK1 in breast cancer is required for tumor cell proliferation and chemoresistance. Two compounds, CILK1-C30 and CILK1-C28, were identified with selective inhibitory effects towards the Tyr-159/Thr-157 dual-phosphorylation of CILK1, pharmacological inhibition of CILK1 significantly suppressed tumor cell proliferation and overcame chemoresistance in multiple experimental models. Large-scale screen of CILK1 substrates confirmed that the kinase directly phosphorylates ERK1, which is responsible for CILK1-mediated oncogenic function. CILK1 is also indicated to be responsible for the chemoresistance of small-cell lung cancer cells. Our data highlight the importance of CILK1 in cancer, implicating that targeting CILK1/ERK1 might offer therapeutic benefit to cancer patients.

Keywords: Breast cancer, CILK1, ERK1, Proliferation, Chemoresistance

Citation styles

APA
He, Y., Zhang, X., Pan, W., Zhang, J., Zhu, W., Zhang, J., Shi, J. (2024). Ciliogenesis-associated Kinase 1 Promotes Breast Cancer Cell Proliferation and Chemoresistance via Phosphorylating ERK1. International Journal of Biological Sciences, 20(7), 2403-2421. https://doi.org/10.7150/ijbs.87442.

ACS
He, Y.; Zhang, X.; Pan, W.; Zhang, J.; Zhu, W.; Zhang, J.; Shi, J. Ciliogenesis-associated Kinase 1 Promotes Breast Cancer Cell Proliferation and Chemoresistance via Phosphorylating ERK1. Int. J. Biol. Sci. 2024, 20 (7), 2403-2421. DOI: 10.7150/ijbs.87442.

NLM
He Y, Zhang X, Pan W, Zhang J, Zhu W, Zhang J, Shi J. Ciliogenesis-associated Kinase 1 Promotes Breast Cancer Cell Proliferation and Chemoresistance via Phosphorylating ERK1. Int J Biol Sci 2024; 20(7):2403-2421. doi:10.7150/ijbs.87442. https://www.ijbs.com/v20p2403.htm

CSE
He Y, Zhang X, Pan W, Zhang J, Zhu W, Zhang J, Shi J. 2024. Ciliogenesis-associated Kinase 1 Promotes Breast Cancer Cell Proliferation and Chemoresistance via Phosphorylating ERK1. Int J Biol Sci. 20(7):2403-2421.

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