المؤلفون: Guddeti, Rohith Kumar, Pacharla, Himavani, Yellapu, Nanda Kumar, Karyala, Prashanthi, Pakala, Suresh B.

المصدر: Medical Oncology; Mar2023, Vol. 40 Issue 3, p1-11, 11p

مستخلص: Cancer cell proliferation is a high energy demanding process, where the cancer cells acquire 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 co-localizes 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 (PFKP) type 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. [ABSTRACT FROM AUTHOR]

: Copyright of Medical Oncology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Saroha, Himanshu Singh, Kumar Guddeti, Rohith, Jacob, Jasmine P., Kumar Pulukuri, Kiran, Karyala, Prashanthi, Pakala, Suresh B.

المصدر: Medical Oncology; Sep2022, Vol. 39 Issue 9, p1-11, 11p

مستخلص: Although Microrchidia 2 (MORC2) is overexpressed in many types of human cancer, its role in breast cancer progression remains unknown. Here, we report that the chromatin remodeler MORC2 expression positively correlates with β-catenin expression in breast cancer cell lines and patients. Overexpression of MORC2 augmented the expression of β-catenin and its target genes, cyclin D1 and c-Myc. Consistent with these results, we found MORC2 knockdown resulted in decreased expression of β-catenin and its target genes. Surprisingly, we observed that c-Myc, the target gene of β-catenin, regulated the MORC2-β-catenin signaling axis through a feedback mechanism. We demonstrated that MORC2 regulates β-catenin expression and function by modulating the phosphorylation of AKT. In addition, we observed reduced proliferation and migration of MORC2 overexpressing breast cancer cells upon β-catenin inhibition. Overall, our results demonstrate that MORC2 promotes breast cancer cell proliferation and migration by regulating β-catenin signaling. [ABSTRACT FROM AUTHOR]

: Copyright of Medical Oncology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)