Metastasis-Associated Protein 1/Nucleosome Remodeling and Histone Deacetylase Complex in Cancer

Abstract

Cancer cells frequently exhibit deregulation of coregulatory molecules to drive the process of growth and metastasis. One such group of ubiquitously expressed coregulators is the metastasis-associated protein (MTA) family, a critical component of nucleosome remodeling and histone deacetylase (NuRD) complex. MTA1 occupies a special place in cancer biology due to its dual corepressor or coactivator nature and widespread overexpression in human cancers. Here, we highlight recent advances in our understanding of the vital roles of MTA1 on transformation, epithelial-mesenchymal transition, and on the functions of key cancer-relevant molecules as a nexus of multiple oncogenes and tumor suppressors. In addition to its paramount role in oncogenesis, we also reveal several new physiological functions of MTA1, related to DNA-damage, inflammatory responses and infection, in which MTA1 functions as a permissive “gatekeeper” for cancer-causing parasites. Further, these discoveries unraveled the versatile multidimensional modes of action of MTA1, which are independent of the NuRD complex and/or transcription. Given the emerging roles of MTA1 in DNA repair, inflammation, and parasitism, we discuss the possibility of MTA1 targeted therapy for use in not only combating cancer but also other inflammation and pathogen-driven pathological conditions.

The Role of micro RNAs in Breast Cancer Metastasis: Preclinical Validation and Potential Therapeutic Targets

“…miR-421 targets metastasis-associated protein-1 (MTA-1), which is involved in chromatin remodeling (157). miR-421 knock-down leads to invasion and metastasis of MCF-7 cells and overexpression in MDA-MB-231 cells suppresses invasion and metastasis (156).…”

Associations between the expression of MTA1 and VEGF-C in esophageal squamous cell carcinoma with lymph angiogenesis and lymph node metastasis

“…Tumor metastasis-related gene 1 (MTA1) occupies a specific position in the entire tumor metastasis-related gene family. A previous study demonstrated that MTA1 protein is a subunit of the nucleosome remodeling and histone deacetylase NuRD (7). It regulates the state of histone deacetylase (HDAC) and nucleosomes by interacting with HDAC so as to regulate its biological functions.…”

“…In addition, previous studies have implicated MTA1 in multiple types of cancer, including gastric, colon, breast, non-small cell lung, prostate, ovarian and esophageal cancer, and, head and neck squamous cell carcinoma (8)(9)(10). Previous studies have primarily focused on the role of MTA1 in tumor angiogenesis, suggesting that it serves crucial functions in tumor angiogenesis in addition to promoting the invasion and metastasis of tumors, while its roles in lymph angiogenesis remain unclear (7)(8)(9)(10). Therefore, the present study used immunohistochemistry to detect MTA1, VEGF-C and carcinoembryonic antigen M2A monoclonal antibody (D2-40) in resected tissue …”

Tumour suppressor HLJ1: A potential diagnostic, preventive and therapeutic target in non-small cell lung cancer

“…This complex process involves cell adhesion, degradation of the surrounding extracellular matrix, migration, proliferation at a secondary site, and stimulation of angiogenesis [12,13] . Many studies on cancer metastasis have been conducted, and several molecules that participate in tumour cell invasion and metastasis, such as SLUG, NM23, CD44, MTA1, MMPs, TIMPs, KAI1, E-cadherin, KISS1 and CRMP1, have been identified in various cancer types [14][15][16][17][18] . There is still no effective strategy for preventing or combating these metastatic processes.…”