Mechanism of MTA1 protein overexpression-linked invasion: MTA1 regulation of hyaluronan-mediated motility receptor (HMMR) expression and function.

Abstract

Even though the hyaluronan-mediated motility receptor (HMMR), a cell surface oncogenic protein, is widely up-regulated in human cancers and correlates well with cell motility and invasion, the underlying molecular and nature of its putative upstream regulation remain unknown. Here, we found for the first time that MTA1 (metastatic tumor antigen 1), a master chromatin modifier, regulates the expression of HMMR and, consequently, its function in breast cancer cell motility and invasiveness. We recognized a positive correlation between the levels of MTA1 and HMMR in human cancer. Furthermore, MTA1 is required for optimal expression of HMMR. The underlying mechanism includes interaction of the MTA1·RNA polymerase II·c-Jun coactivator complex with the HMMR promoter to stimulates its transcription. Accordingly, selective siRNA-mediated knockdown of HMMR in breast cancer cells substantially reduces the invasion and migration of cells. These findings reveal a regulatory role for MTA1 as an upstream coactivator of HMMR expression and resulting biological phenotypes.

• Authors: Deivendran Sankaran, Suresh B Pakala, Vasudha S Nair, Divijendra Natha Reddy Sirigiri, Dinesh Cyanam, Ngoc-Han Ha, Da-Qiang Li, T R Santhoshkumar, M Radhakrishna Pillai, Rakesh Kumar
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 287 Issue 8 Pg. 5483-91 (Feb 17 2012) ISSN: 1083-351X [Electronic] United States
• PMID: 22203674 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Retracted Publication)

Chemical References

• Extracellular Matrix Proteins
• Hyaluronan Receptors
• Mta1 protein, human
• Repressor Proteins
• Trans-Activators
• hyaluronan-mediated motility receptor
• JNK Mitogen-Activated Protein Kinases
• RNA Polymerase II
• Histone Deacetylases

Topics

• Animals
• Breast Neoplasms (genetics, metabolism, pathology)
• Carcinoma, Intraductal, Noninfiltrating (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Extracellular Matrix Proteins (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Histone Deacetylases (genetics)
• Humans
• Hyaluronan Receptors (genetics, metabolism)
• JNK Mitogen-Activated Protein Kinases (metabolism)
• Mice
• Neoplasm Invasiveness
• RNA Polymerase II (metabolism)
• Repressor Proteins (genetics)
• Trans-Activators
• Transcription, Genetic (genetics)