The Mechanism Of OVOL2-Mediated Supression Of Fatty Acid Oxidation In Breast Cancer Cells

Fatty acid oxidation is a vital part of metabolic reprogramming that has been recognized as a hallmark of cancer.The hyperactivation of fatty acid oxidation feasts tumor cells with energy and biomolecules that are essential for their rapid proliferation.OVOL2 is an important transcriptional inhibitor that is able to suppress the epithelialmesenchymal transition and impede the progression of cancers such as breast cancer,lung cancer and colon cancer.Although both of fatty acid oxidation and OVOL2 have been regarded as valuable factors in cancer development,the relationship between them remains to be revealed.In this work,we demonstrate the capability of OVOL2 in the suppression of fatty acid oxidation and reprogramming of the energy metabolism in breast cancer cells.In ER+breast cancer cells,OVOL2 directly binds to STAT3 and inhibits its expression;while in triple negative breast cancer cells,OVOL2 hampers the Tyr705 phosphorylation of STAT3 by inhibiting JAK2 expression.In both manners,OVOL2 results in the decline of fatty acid oxidation,decreases the production of intracellular ATP and NADPH/NADP+,but boosts ROS generation.Moreover,we further found that OVOL2 can decrease the stemness of breast cancer cells,inhibit primary tumor growth and pulmonary metastasis in mice.These results imply that different subtypes of breast cancer cells have different ways to regulate fatty acid oxidation,which should be recognized first before the treatment of breast cancer.This work clarifies the role of OVOL2 in tumor energy metabolism,reveals a novel mechanism for tumor suppression by OVOL2,and enriches the biological functions of OVOL2.We expect that our discoveries could deepen the knowledge of breast cancer subtypes,which is of great significance for the precision treatment of breast cancer.