Rakesh Kumar
Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, 2300 Eye Street, N.W., Washington, DC 20037, USA
Fundamental to the process of cancer progression and metastasis is the ability of cancer cells to respond to both extra- and intra-cellular milieu and translate resulting signals for the benefit of gene expression in an orderly manner through chromatin remodeling complexes. The functional outcome of the chromatin remodeling complexes is primarily influenced by the nature of enzymes and coregulatory proteins and its combinatorial post-translational modifications, among other mechanisms. One of such families of master chromatin modifiers is the metastasis tumor antigen (MTA) family, which are an integral part of nucleosome remodeling and histone deacetylation and nucleosome remodeling factor complexes.
The MTA family regulates cellular pathways in both normal and cancer cells by influencing the chromatin status and expression of target genes while influencing nucleosome landscape via interacting with various modified histones. The MTA1, one of the most frequently upregulated oncogenes, is a nodular molecule in the process of tumorigenesis by a number of oncogenes. In general, MTA1 upregulation correlates with an aggressive and invasive phenotypes of tumors and an unfavorable outcome for cancer patients. At the cellular level, MTA1-containing chromatin remodeling complexes regulate a range of processes including, cell survival, invasiveness, transformation, DNA-damage response, angiogenesis, metastasis and therapeutic sensitivity of tumor cells. In addition, MTA1-containing chromatin remodeling complexes represent emerging modifiers of gene expression with functions in embryonic stem-cell differentiation, reprogramming of pluripotent stem cells and mesenchymal nature of stem cells as well as cancer stem cells. For example, MTA1 status has been proposed to be one of critical modifiers of chemo-sensitivity of cancer cells due to MTA1’s ability to support cancer stem cell-like phenotypes. The lecture will provide an overview of the current and future functions of MTA1 in cancer and stem cell biology and underlying molecular mechanisms.