%0 Journal Article
%T Ciliogenesis-associated Kinase 1 Promotes Breast Cancer Cell Proliferation and Chemoresistance via Phosphorylating ERK1.
%A He Y
%A Zhang X
%A Pan W
%A Zhang J
%A Zhu W
%A Zhang J
%A Shi J
%J Int J Biol Sci
%V 20
%N 7
%D 2024
%M 38725848
%F 10.75
%R 10.7150/ijbs.87442
%X 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.