Clinical implications of MTA proteins in human cancer.

Abstract

Metastasis-associated gene or metastasis tumor antigen 1 (MTA1) is a new member of cancer progression-related gene family. It was first identified in rat mammary adenocarcinoma and later recognized as an important constituent of nucleosomal remodeling complex (NuRD), displaying dual regulatory functions as a co-repressor and co-activator for a large number of genes. Chromatin remodelers are ATP-dependent multi-protein chromatin modifying machines. These complexes alter the nucleosome positioning regulating the accessibility of genomic DNA to various transcription factors and thus modulate eukaryotic gene transcription. Since its identification two decades ago, MTA1 has been reported to be overexpressed in many cancers. Moreover, its overexpression has also been correlated with transformation and tumor progression. Furthermore, MTA1 has been shown to modulate the response of several tumor suppressor genes like p53 and oncogenes like c-myc. Taken together, current literature suggests that MTA proteins, especially MTA1, act as a master co-regulatory molecule involved in the carcinogenesis and progression of various malignant tumors. The primary focus of this review is to provide an overview of the MTA proteins with special emphasis on its role in cancer and use as a marker for cancer progression and potential target for therapy.