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

## TL;DR

This study shows that CILK1 promotes breast cancer growth and drug resistance by phosphorylating ERK1, suggesting it could be a new target for cancer therapy.

## Contribution

The study identifies CILK1 as a novel driver of breast cancer proliferation and chemoresistance through ERK1 phosphorylation.

## Key findings

- High CILK1 expression is required for breast cancer cell proliferation and chemoresistance.
- Pharmacological inhibition of CILK1 suppresses tumor growth and overcomes drug resistance in experimental models.
- CILK1 directly phosphorylates ERK1, linking it to oncogenic activity in breast and lung cancer cells.

## 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.