The chromatin modifier MORC2 affects glucose metabolism by regulating the expression of lactate dehydrogenase A through a feed forward loop with c‐Myc

• Published in: FEBS letters 2021-05, Vol.595 (9), p.1289-1302
• Main Authors: Guddeti, Rohith Kumar, Thomas, Liz, Kannan, Anbarasu, Karyala, Prashanthi, Pakala, Suresh B., Nebreda, Angel
• Format: Article
• Language: English
• Subjects: c‐Myc; glucose metabolism; LDHA; MORC2
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1002/1873-3468.14062

Microrchidia family CW‐type zinc finger 2 (MORC2) is a recently identified chromatin modifier with an emerging role in cancer metastasis. However, its role in glucose metabolism, a hallmark of malignancy, remains to be explored. We found that MORC2 is a glucose‐inducible gene and a target of c‐Myc. Our meta‐analysis revealed that MORC2 expression is positively correlated with the expression of enzymes involved in glucose metabolism in breast cancer patients. Furthermore, overexpression of MORC2 in MCF‐7 and BT‐549 cells augmented the expression and activity of a key glucose metabolism enzyme, lactate dehydrogenase A (LDHA). Conversely, selective knockdown of MORC2 by siRNA markedly decreased LDHA expression and activity and in turn reduced cancer cell migration. Collectively, these findings provide evidence that MORC2, a glucose‐inducible gene, modulates the migration of breast cancer cells through the MORC2–c‐Myc–LDHA axis.