­­­MORC2 interaction with MAX contributes to the expression of Glycolytic enzymes, Breast Cancer Cell Proliferation and Migration

Abstract

Cancer cell proliferation is a high energy demanding process, where the cancer cells acquire the energy by high rates of glycolysis, and this phenomenon is known as the “Warburg effect”. Microrchidia 2 (MORC2), an emerging chromatin remodeler, is over expressed in several cancers including breast cancer, and found to promote cancer cell proliferation. However, the role of MORC2 in glucose metabolism in cancer cells remains unexplored. In this study, we report that MORC2 interacts indirectly with the genes involved in glucose metabolism via transcription factors MAX (MYC-associated factor X) and MYC. We also found that MORC2 colocalizes and interacts with MAX. Further, we observed a positive correlation of expression of MORC2 with glycolytic enzymes Hexokinase 1 (HK1), Lactate dehydrogenase A (LDHA) and Phosphofructokinase platelet type (PFKP) in multiple cancers. Surprisingly, the knockdown of either MORC2 or MAX not only decreased the expression of glycolytic enzymes but also inhibited breast cancer cell proliferation and migration. Together, these results demonstrate the involvement of the MORC2/MAX signaling axis in the expression of glycolytic enzymes and breast cancer cell proliferation and migration.