المؤلفون: Vattem, Chaitanya¹ (AUTHOR), Pakala, Suresh B¹ (AUTHOR) pakalasb@iisertirupati.ac.in

المصدر: Journal of Biosciences. 4/15/2022, Vol. 47 Issue 2, p1-23. 23p.

مصطلحات موضوعية: *DNA repair, *CELLULAR signal transduction, *DNA damage, *PROTEINS, *CELL proliferation, *CANCER cells, *CELL migration

مستخلص: Metastasis-associated protein 1 (MTA1) is an emerging transcriptional co-regulator and was found to be aberrantly expressed in different types of cancers. MTA1 has been reported to regulate multiple cancer-related signalling pathways leading to tumour progression and metastasis. Recently, MTA1 was also implicated in cancer metabolism, where it was found to regulate the 'Warburg effect' to drive breast cancer cell invasion. Overall, the functional dynamism of MTA1 can be attributed to its dual co-regulatory effects in regulating a diverse array of target genes involved in cell proliferation, DNA damage repair, angiogenesis, invasion, migration, metastasis, and metabolism in different types of cancers. In this review, we have attempted to provide a brief summary of MTA1 as a modulator of the hallmarks of cancer. [ABSTRACT FROM AUTHOR]

المؤلفون: Ohshiro, Kazufumi, Rayala, Suresh K., Wigerup, Caroline, Pakala, Suresh B., Natha, Reddy S Divijendra, Gururaj, Anupama E., Molli, Poonam R., Månsson, Sofie Svensson, Ramezani, Ali, Hawley, Robert G., Landberg, Goran, Lee, Norman H., Kumar, Rakesh

المصدر: Ohshiro , K , Rayala , S K , Wigerup , C , Pakala , S B , Natha , R S D , Gururaj , A E , Molli , P R , Månsson , S S , Ramezani , A , Hawley , R G , Landberg , G , Lee , N H & Kumar , R 2010 , ' Acetylation-dependent oncogenic activity of metastasis-associated protein 1 co-regulator ' , EMBO reports , vol. 11 , no. 9 , pp. 691-697 . https://doi.org/10.1038/embor.2010.99Test

مصطلحات موضوعية: Lys 626 acetylation, MTA1, Raf1 activation, Ras, transformation

الوصف: High expression of metastasis-associated protein 1 co-regulator (MTA1), a component of the nuclear remodelling and histone deacetylase complex, has been associated with human tumours. However, the precise role of MTA1 in tumorigenesis remains unknown. In this study, we show that induced levels of MTA1 are sufficient to transform Rat1 fibroblasts and that the transforming potential of MTA1 is dependent on its acetylation at Lys626. Underlying mechanisms of MTA1-mediated transformation include activation of the Ras-Raf pathway by MTA1 but not by acetylation-inactive MTA1; this was due to the repression of G ±i2 transcription, which negatively influences Ras activation. We observed that acetylated MTA1-histone deacetylase (HDAC) interaction was required for the recruitment of the MTA1-HDAC complex to the G ±i2 regulatory element and consequently for the repression of G ±i2 transcription and expression leading to activation of the Ras-Raf pathway. The findings presented in this study provide for the first time-to the best of our knowledge-evidence of acetylation-dependent oncogenic activity of a cancer-relevant gene product. © 2010 European Molecular Biology Organization.

الإتاحة: https://doi.org/10.1038/embor.2010.99Test
https://research.manchester.ac.uk/en/publications/21019312-9fbc-4957-af87-0cf0d03c7a38Test

المؤلفون: Guddeti, Rohith Kumar¹ (AUTHOR), Bali, Prerna¹ (AUTHOR), Karyala, Prashanthi² (AUTHOR), Pakala, Suresh B.¹ (AUTHOR) pakalasb@iisertirupati.ac.in

المصدر: Biochemical & Biophysical Research Communications. Nov2019, Vol. 520 Issue 1, p54-59. 6p.

مصطلحات موضوعية: *BREAST cancer, *GLUCOSE metabolism, *CELL motility, *CELL migration, *CHROMATIN

مستخلص: 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. [ABSTRACT FROM AUTHOR]