MTA1 coregulator regulates LDHA expression and function in breast cancer

Metastasis Associated Protein1 (MTA1) is a chromatin modifier and its expression is significantly associated with prognosis of many cancers. However, its role in glucose metabolism remains unexplored. Here, we report that MTA1 has a significant role in glucose metabolism where MTA1 regulates the LDH...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2019-11, Vol.520 (1), p.54-59
Main Authors: Guddeti, Rohith Kumar, Bali, Prerna, Karyala, Prashanthi, Pakala, Suresh B.
Format: Article
Language:English
Subjects:
Breast cancer
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Movement
Female
Gene Expression Regulation, Neoplastic
Glucose - metabolism
Glycolysis
Histone Deacetylases - metabolism
Humans
L-Lactate Dehydrogenase - metabolism
LDHA and glucose metabolism
MCF-7 Cells
Molecular Docking Simulation
MTA1
Neoplasm Invasiveness
Promoter Regions, Genetic
Proto-Oncogene Proteins c-myc - metabolism
Repressor Proteins - metabolism
RNA, Small Interfering - metabolism
Signal Transduction
Trans-Activators - metabolism
Transcription, Genetic
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Summary:Metastasis Associated Protein1 (MTA1) is a chromatin modifier and its expression is significantly associated with prognosis of many cancers. However, its role in glucose metabolism remains unexplored. Here, we report that MTA1 has a significant role in glucose metabolism where MTA1 regulates the LDHA expression and activity and subsequently its function in breast cancer motility. The results showed that MTA1 expression is positively correlated with the LDHA expression levels in breast cancer patients. Further, it was found that MTA1 is necessary for the optimal expression of LDHA. The underlying molecular mechanism involves the interaction of MTA1 with c-Myc and recruitment of MTA1-c-Myc complex on to the LDHA promoter to regulate its transcription. Consequently, the LDHA knock down using LDHA specific siRNA in MCF7 cells stably expressing MTA1 reduced the migration of MCF7 cells. Altogether these findings revealed the regulatory role for MTA1 in LDHA expression and its resulting biological function. •MTA1 interacts with the genes of glucose metabolism.•MTA1 regulates LDHA expression and its activity.•MTA1 interacts with c-Myc.•LDHA mediates MTA1 mediated cell motility.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2019.09.078