A Molecular Study of Activating Transcription Factor 3 and its Interacting Proteins in Breast Cancer Cells

Abstract

Breast cancer (BC) has emerged as the majorly occurring cancer worldwide, by surpassing lung cancer with an estimation of 2.3 million new cases (11.7%). BC, being of a distinct heterogeneous nature, shows unique phenotypic variation, and the most ruinous state of breast carcinoma is the metastatic condition of cancer. BC metastasis is tissue-specific and complex that involves the association between several genes or prime factors or various signaling effectors existing in the tumor microenvironment. ATF3 [activating transcription factor 3], a constituent of AP-1 [activating protein-1] family plays a predominant role in BC progression. ATF3 is a signal inducing protein, and its expression is stimulated by various factors such as DNA damage, anoxia, hypoxia, and cytokines. Transforming growth factor-beta1 (TGF-and#946;1), a predominant cytokine, acts as the known growth inhibitor under physiological conditions, whereas in BC, the loss of this tumour-suppressive nature results in proliferative effects, leading to BC metastasis. ATF3 is stimulated by TGF-and#946;1 in a protracted and relentless manner in hBCs [human breast cancer cells; MDA-MB231] in contrast to an ephemeral expression in normal breast epithelial cells [MCF-10A]. The protracted and relentless expression of ATF3 could mediate BC progression by activation of genes like the cell cycle gene (cyclin A1), invasive gene (matrix metalloproteinase 13; MMP13), and metastasis gene (Runx2). The mechanisms of how TGF-and#946;1 stabilizes ATF3 and its association with other proteins in hBCs at molecular level are yet to be reported. Thus, the study focuses on identifying and characterizing the TGF-and#946;1-stimulation of posttranslational modifications (PTMs) and the interacting proteins of ATF3, which may provide a better understanding of the regulation of BC-mediated bone metastasis newline