SIKs suppress tumor function and regulate drug resistance in breast cancer.

Salt-inducible kinases (SIKs), belonging to an AMP-activated kinase (AMPK) family, have an evolving role in tumourigenesis and metastasis in many solid tumours. However, the function of SIKs in breast cancer is not fully established. Here, we systematically elucidated the function of SIK family members in breast cancer. In clinical cohort of breast cancer, the expression of SIK1, SIK2 and SIK3 increased expression of SIKs was associated with good clinical outcome in breast cancer cohort. In vitro, reduced expression of SIK2 and SIK3, by way of knockdown increased the proliferation of breast cancer cells. However, SIK2 and SIK3 had contrasting effects on adhesion in breast cancer cells. Knockdown of SIK2 only enhanced the adhesion of triple negative breast cancer cell, while knockdown of SIK3 can decrease the adhesion of both MDA-MB-231 and MCF-7 cells. Interestingly, knockdown of SIK1 and SIK3 was seen to increase the invasion of MDA-MB-231 cells. Furthermore, reduced SIKs, even triple knockdown of SIK1, SIK2 and SIK3 rendered the breast cancer cells to confer chemoresistance to paclitaxel and cisplatin. Collectively, the study reports that SIKs are actively involved in regulating the aggressive functions of breast cancer cells and influence the clinical course of the patients with breast cancer that they molecules are potential prognostic factors and chemotherapy biomarkers.