Chemerin Enhances Migration and Invasion of OC Cells via CMKLR1/RhoA/ROCK-Mediated EMT.

Abstract

Chemerin is a newly described adipokine with significant effects on obesity, metabolic disorders, and immune trafficking. Recently, chemerin has gained prominence for its potential roles in cancer and tumorigenesis with pro- or antitumor effects. To date, most referenced multifunctions of chemerin are attributed to the chemokine-like receptor 1 (CMKLR1), distributing broadly in many tissues. This study investigates the in vitro roles of chemerin treatment on migration and invasion of ovarian carcinoma cells (OVCAR-3 and SK-OV-3) and potential underlying mechanisms. Herein, exogenous chemerin treatment promotes growth and invasion of SK-OV-3 cells but has no significant effects on OVCAR-3 cells. SK-OV-3 cells undergo morphological elongation characterized by epithelial-to-mesenchymal transition (EMT) and Ras homologous genome members A (RhoA)/Rho protein-related curl spiral kinase-1 (ROCK1) activation. Furthermore, chemerin-enhanced invasion and EMT of SK-OV-3 cells are effectively blocked by C3 transferase (C3T) and Y27632 and RhoA and ROCK1 inhibitor, respectively. More importantly, RhoA/ROCK1-EMT-mediated SK-OV-3 cell invasion is orchestrated by CMKLR1 upregulation after chemerin treatment (50 ng/mL). The silencing of CMKLR1 significantly (P < 0.0001) reverses the chemerin-enhanced invasion, EMT, and RhoA/ROCK1 activation of SK-OV-3 cells. Our study indicates that chemerin promotes invasion of OC cells via CMKLR1-RhoA/ROCK1-mediated EMT, offering a novel potential target for metastasis of OC.