1. MARK2 potentiate aerobic glycolysis-mediated cell growth in breast cancer through regulating mTOR/HIF-1α and p53 pathways.
- Author
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Ponnusamy L, Natarajan SR, and Manoharan R
- Subjects
- Cell Line, Tumor, Cell Proliferation, Female, Glycolysis, Humans, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, TOR Serine-Threonine Kinases genetics, TOR Serine-Threonine Kinases metabolism, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Breast Neoplasms genetics, Breast Neoplasms metabolism, Protein Serine-Threonine Kinases genetics
- Abstract
The microtubule-affinity regulating kinases (MARKs) family plays a crucial role in regulating breast cancer development and progression. However, its precise function and the relevant molecular mechanism in breast cancer have not yet been elucidated. In this study, analysis of The Cancer Genome Atlas (TCGA) data revealed that MARK2 expression was markedly upregulated in breast cancer tissues, and high expression of MARK2 was correlated with poor survival. Functional assays showed that MARK2 deletion or inhibition suppressed aerobic glycolysis and cell growth as well as induced cell cycle arrest and apoptosis in breast cancer cells. Mechanistically, MARK2 stimulates mTOR-mediated hypoxia-inducible factor 1 alpha (HIF-1α) transcription activity and represses p53-transcription activity in breast cancer cells. TCGA data revealed that MARK2 expression was positively correlated with mTOR, Raptor, S6K1, glucose transporter 1, lactate dehydrogenase, HIF-1α, and 4E-BP1 expression, whereas negatively correlated with p53, p21, and Bax in breast cancer tissue. Conclusively, our study demonstrated that MARK2 promotes breast cancer aerobic glycolysis and cell proliferation, and inhibits apoptosis, in part, through regulating mTOR/HIF-1α and p53 signaling pathways. Overall, these findings point to the potential of targeting MARK2 for breast cancer treatment., (© 2022 Wiley Periodicals LLC.)
- Published
- 2022
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