Perspective on targeting salt-inducible kinase 2 (SIK2) in ovarian cancer metastasis

Abstract

: Ovarian cancer has a predilection for metastasis to the omentum in abdominal cavity. Omental adipocytes have been shown to secret adipokines to attract implantation of ovarian cancer cells and provide free fatty acids to promote rapid growth of omental metastases. However, how ovarian cancer cells take advantage of the adipocyte-rich metastatic niche is not understood. In a recent report by Miranda and colleagues published in Cancer Cell, they show that salt-inducible kinase 2 (SIK2) is overexpressed in omental metastases compared with primary tumors. Omental adipocytes activate SIK2 in co-cultured ovarian cancer cells, leading to increased fatty acid oxidation and proliferation of ovarian cancer cells. Inhibition of SIK2 significantly reduces growth of metastases in omentum and other adipocyte-rich tissues. These findings identify SIK2 as a highly promising target in suppressing ovarian cancer metastasis. This perspective will describe the current understanding of the molecular mechanisms by which SIK2 promotes ovarian cancer metastasis and discuss the promise of targeting SIK2 in improving the therapeutic efficacy of chemotherapy.