Anti-Cancer Drug Discovery & Therapy (Track)


Suresh B. Pakala, Suresh K. Rayala, Kazufumi Ohshiro, Prakriti Mudvari, Sirigiri Divijendra Natha Reddy and Rakesh Kumar

Department of Biochemistry and Molecular Biology, The George Washington University, Medical Center, Washington, District of Columbia 20037, USA


Breast cancer is the most common cancer diagnosed among women, accounting for an increasing trend in cancer death among women. The breast cancer metastasis to the distant sites, including to lungs, constitutes one of the major causes of mortality in breast cancer patients. Among other mechanisms, cancer metastasis is profoundly influenced by misregulation signaling and regulatory factors, leading to abnormal expression of certain gene products, and hence, resulting biologic functions. The transcription of critical genes by tightly regulated by chromatin remodeling complexes and/or its components. In recent years, one of such regulatory molecule, the metastasis tumor antigen 1 (MTA1) has emerged as a global modifier of gene transcription by virtue of its role in remodeling the chromatin in the proximity of the target genes. In spite of a large body of work in support of MTA1 overexpresion in human cancer and tumor aggressiveness, the contribution of the physiological level of MTA1 in breast-to-lung metastasis continues to be unknown. Here we attempt to investigate this outstanding question in the field by investigating the influence of selective genetic depletion of MTA1 on breast-to-lung metastasis. Here we found that MTA1 acts as a mandatory modifier of breast-to-lung metastasis. The underlying mechanism involves MTA1 stimulation of a DNA-binding transcription factor and in-turn, the expression and functions of target genes. Results from a physiologically relevant whole animal model corroborate well with the levels of MTA1 and target transcription factor in the publically available cancer data sets. In brief, our study has revealed an essential modifying role of the physiologic level of MTA1 in promoting/supporting breast-to-lung metastasis.