The Metastasis-Associated Gene MTA3, a Component of the Mi-2/NuRD Transcriptional Repression Complex, Predicts Prognosis of Gastroesophageal Junction Adenocarcinoma

Abstract

Gastroesophageal junction (GEJ) adenocarcinoma carries a poor prognosis that is largely attributable to early and frequent metastasis. The acquisition of metastatic potential in cancer involves epithelial-to-mesenchymal transition (EMT). The metastasis-associated gene MTA3, a novel component of the Mi-2/NuRD transcriptional repression complex, was identified as master regulator of EMT through inhibition of Snail to increase E-cadherin expression in breast cancer. Here, we evaluated the expression pattern of the components of MTA3 pathway and the corresponding prognostic significance in GEJ adenocarcinoma. MTA3 expression was decreased at both protein and mRNA levels in tumor tissues compared to the non-tumorous and lowed MTA3 levels were noted in tumor cell lines with stronger metastatic potential. Immunohistochemical analysis of a cohort of 128 cases exhibited that patients with lower expression of MTA3 had poorer outcomes. Combined misexpression of MTA3, Snail and E-cadherin had stronger correlation with malignant properties. Collectively, results suggest that the MTA3-regulated EMT pathway is altered to favor EMT and, therefore, disease progression and that MTA3 expression was an independent prognostic factor in patients with GEJ adenocarcinoma.

MTA3 regulates malignant progression of colorectal cancer through Wnt signaling pathway

“…12 In addition, MTA3 expression was an independent prognostic factor in patients with gastroesophageal junction adenocarcinoma. 13 To date, its clinical significance and biological characteristics in colorectal carcinoma have not been well investigated. In this study, we demonstrated MTA3 protein expression was higher in CRC tissues than that in normal colon tissues.…”

The oncogenic roles of nuclear receptor coactivator 1 in human esophageal carcinoma

“…Functionally, sex steroid receptors such as estrogen receptor (ER) and androgen receptor (AR) serve as transcription factors by recruiting multiple coactivators . By collaborating with transcription factors, coactivators play crucial roles in chromatin remodeling and regulation of gene expression . Nuclear receptor coactivator 1 (NCOA1, also known as SRC‐1) is the founding member of the nuclear receptor coactivator family .…”

“…4,5 By collaborating with transcription factors, coactivators play crucial roles in chromatin remodeling and regulation of gene expression. [6][7][8][9][10][11][12] Nuclear receptor coactivator 1 (NCOA1, also known as SRC-1) is the founding member of the nuclear receptor coactivator family. 2,13 In addition to serving as a coactivator of AR 14,15 and ER, 16,17 NCOA1 is also involved in transcriptional regulation of genes by interacting with other transcriptional factors.…”

Novel TG‐FGFR1 and TRIM33‐NTRK1 transcript fusions in papillary thyroid carcinoma

“…The MTA3 gene is a member of the metastasis‐associated protein family, identified as key regulators of the epithelial‐mesenchymal transition process and E‐cadherin expression . MTA3 has been described to be under‐expressed in some malignancies, including breast cancer, ovarian cancer, gastroesophageal junction adenocarcinoma or endometrial cancer, and even as a suppressor of metastases in these tumors . Shan et al described decreased MTA3 expression in glioma and its association with prognosis, which suggests that MTA3 is a suppressor gene in this malignancy.…”