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MORC2/β-catenin signaling axis promotes proliferation and migration of breast cancer cells

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Abstract

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.

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Acknowledgements

We are thankful to IISER Tirupati for providing the financial support. RKG is thankful to DBT for awarding SRF and providing the financial support.

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Authors and Affiliations

  1. Department of Biology, Indian Institute of Science Education and Research (IISER) Tirupati, Karakambadi Road, Mangalam, Tirupati, Andhra Pradesh, 517507, India

    Himanshu Singh Saroha, Rohith Kumar Guddeti & Suresh B. Pakala

  2. Department of Chemistry, Indian Institute of Science Education and Research (IISER) Tirupati, Karakambadi Road, Mangalam, Tirupati, Andhra Pradesh, 517507, India

    Jasmine P. Jacob & Kiran Kumar Pulukuri

  3. Department of Biotechnology, Faculty of Life and Allied Health Sciences, Ramaiah University of Applied Sciences, Bengaluru, 560054, India

    Prashanthi Karyala

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  1. Himanshu Singh Saroha
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Contributions

HSS, RKG, JPJ, KKP, PK, and SBP performed experiments and analyzed data. SBP supervised the entire project, and designed the experiments. HSS, RKG, and SBP wrote the paper. All authors read and approved the final manuscript.

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Correspondence to Suresh B. Pakala.

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Saroha, H.S., Kumar Guddeti, R., Jacob, J.P. et al. MORC2/β-catenin signaling axis promotes proliferation and migration of breast cancer cells. Med Oncol 39, 135 (2022). https://doi.org/10.1007/s12032-022-01728-6

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