MTA1 coregulator regulates LDHA expression and function in breast cancer
Rohith Kumar Guddeti1, Prerna Bali1, Prashanthi Karyala2
1Biology Division, Indian Institute of Science Education and Research (IISER) Tirupati, Karakambadi Road, Mangalam, Tirupati, 517507, Andhra Pradesh, India.
Biochemical and Biophysical Research Communications
|October 2, 2019
Summary
Metastasis Associated Protein 1 (MTA1) regulates lactate dehydrogenase A (LDHA) expression and activity, impacting breast cancer cell motility. This study uncovers MTA1's role in glucose metabolism and cancer progression.
Area of Science:
- Cancer Biology
- Molecular Oncology
- Metabolic Regulation
Background:
- Metastasis Associated Protein 1 (MTA1) is a chromatin modifier linked to cancer prognosis.
- The role of MTA1 in glucose metabolism is not well understood.
- Investigating MTA1's function in cancer metabolism is crucial for understanding tumor progression.
Purpose of the Study:
- To elucidate the role of MTA1 in glucose metabolism.
- To determine if MTA1 influences lactate dehydrogenase A (LDHA) expression and activity.
- To explore the mechanism by which MTA1 affects breast cancer cell motility.
Main Methods:
- Correlation analysis of MTA1 and LDHA expression in breast cancer patients.
- Investigating MTA1's necessity for LDHA expression.
- Identifying molecular interactions between MTA1, c-Myc, and the LDHA promoter.
- LDHA knockdown experiments using siRNA in MCF7 cells.
Main Results:
- MTA1 expression positively correlates with LDHA levels in breast cancer.
- MTA1 is essential for optimal LDHA expression.
- MTA1 interacts with c-Myc to regulate LDHA transcription via promoter recruitment.
- LDHA knockdown in MTA1-expressing MCF7 cells reduced cell migration.
Conclusions:
- MTA1 plays a significant role in regulating LDHA expression and activity.
- MTA1 influences breast cancer cell motility through modulation of LDHA.
- The MTA1-c-Myc complex is a key regulator of LDHA transcription in breast cancer.
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