Journal Article

SIK2 promotes ovarian cancer cell motility and metastasis by phosphorylating MYLK

Lu, Zhen, Yu, Xuejiao, Zhang, Lin, Wang, Juan, Bast, Robert C., Shi, Xiu, Fu, Fengqing, Chen, Youguo, Zou, Xinwei, Zhou, Jinhua, Li, Qiutong, Bian, Shimin, Guo, Lingchuan

2022

Overview

Salt‐inducible kinase 2 (SIK2; also known as serine/threonine‐protein kinase SIK2) is overexpressed in several cancers and has been implicated in cancer progression. However, the mechanisms by which SIK2 regulates cancer cell motility, migration and metastasis in ovarian cancer have not been fully discovered. Here, we identify that SIK2 promotes ovarian cancer cell motility, migration and metastasis in vitro and in vivo. Mechanistically, SIK2 regulated cancer cell motility and migration by myosin light chain kinase, smooth muscle (MYLK)‐meditated phosphorylation of myosin light chain 2 (MYL2). SIK2 directly phosphorylated MYLK at Ser343 and activated its downstream effector MYL2, promoting ovarian cancer cell motility and metastasis. In addition, we found that adipocytes induced SIK2 phosphorylation at Ser358 and MYLK phosphorylation at Ser343, enhancing ovarian cancer cell motility. Moreover, SIK2 protein expression was positively correlated with the expression of MYLK‐pS343 in ovarian cancer cell lines and tissues. The co‐expression of SIK2 and MYLK‐pS343 was associated with reduced median overall survival in human ovarian cancer samples. Taken together, SIK2 positively regulates ovarian cancer motility, migration and metastasis, suggesting that SIK2 is a potential candidate for ovarian cancer treatment. SIK2 is overexpressed in several cancers and has been implicated in cancer progression. However, the mechanisms by which SIK2 regulates cancer cell motility and metastasis in ovarian cancer (OC) have not been fully described. Here, we have identified that SIK2 promotes OC cell motility and metastasis by phosphorylating MYLK/MYL2, suggesting that SIK2 may serve as a potential target in OC treatment.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Adenosine triphosphate / Adipocytes / Antibodies / Biotechnology / Cell adhesion & migration / Cell migration / cell motility / Cloning / Ethylenediaminetetraacetic acid / Kinases / Laboratories / Life sciences / Mass spectrometry / Metastases / Metastasis / Motility / Muscle proteins / MYLK / Myosin / Myosin-light-chain kinase / Ovarian cancer / Peptides / Phosphorylation / Protein kinase / Protein kinases / Proteins / Reagents / Scientific imaging / SIK2 / Smooth muscle / Stains & staining / Threonine / Tumor cell lines / Wound healing