PMEPA1 induces EMT via a non‐canonical TGF‐β signalling in colorectal cancer

Abstract

Prostate transmembrane protein androgen induced 1 (PMEPA1) has been reported to promote cancer progression. Metastasis is the main factor leading to cancer progression and poor prognosis, and at the beginning of metastasis, epithelial‐to‐mesenchymal transition (EMT) is a crucial activation. However, the relationship between PMEPA1 and EMT in colorectal cancer metastasis is still poorly understood. In this study, we first testified that PMEPA1 expresses higher in tumour than normal tissue in Gene Expression Omnibus database, in the Cancer Genome Atlas (TCGA) as well as in the clinical data we collected. Moreover, the higher expression was associated with poor prognosis. We furthermore demonstrated PMEPA1 promotes colorectal cancer metastasis and EMT in vivo and in vitro. We found that PMEPA1 activates the bone morphogenetic proteins (BMP) signalling of TGF‐β signalling resulting in promoting EMT and accelerating the proliferation and metastasis of colorectal cancer.

Analysis of PMEPA1 Isoforms (a and b) as Selective Inhibitors of Androgen and TGF-β Signaling Reveals Distinct Biological and Prognostic Features in Prostate Cancer

“…Earlier data from several laboratories indicated both pro-oncogenic and tumor growth inhibitory functions of the PMEPA1 gene in various solid tumors, including cancers of the breast, lung, colon and prostate [11,14,16,19,20,[24][25][26][27][28][29][30][31][32][33][34]. Our data on distinct expressions and regulations of PMEPA1 gene isoforms (a and b) have underscored the rationale for evaluating isoform specific functions in prostate tumorigenesis and progression.…”

Cyclooxygenase 2-Regulated Genes an Alternative Avenue to the Development of New Therapeutic Drugs for Colorectal Cancer

“…Furthermore, PMEPA1 is involved in differentiation of colon epithelial cells and high levels are also found in all phases of CRC development, including metastasis, in patients (Brunschwig et al, 2003). Furthermore, its high expression in CRC is related to poor prognosis and postulated as a predictor of relapse risk (Xu et al, 2017;Zhang et al, 2019). PMEPA1 is also overexpressed in intestinal tumors in Apc (Min) mice, which are prone to intestinal adenoma formation and is also dysregulated in human CRC adenomas (Reichling et al, 2005).…”

“…A recent study using colon cancer cell lines revealed the role of PMEPA1 in cell migration and invasion through bone morphogenetic proteins (BMP) signaling pathway activation and phosphorylation of the transcription factors Smad1 and Smad5 (Zhang et al, 2019), which also correlates with its described effect in ovarian cancer cells (Jimenez-Segovia et al, 2019). NEDD9 (Neural Precursor Cell Expressed, Developmentally Down-Regulated-9) or HEF1 (Human enhancer of filamentation 1) is a structural protein mainly found in epithelial cells, which is upregulated by TGF-b and expressed transiently during embryonic life in mice.…”

GGCT promotes colorectal cancer migration and invasion via epithelial‑mesenchymal transition

“…It has recently been accepted that EMT is an important and complex phenomenon that determines the aggressiveness of colon cancer (27). Zhang et al (20) demonstrated that Prostate Transmembrane Protein, Androgen Induced 1 induced EMT via a non-canonical transforming growth factor-β signaling pathway in CRC, and Wei et al (28) indicated that FAT Atypical Cadherin 4 modulated CRC tumorigenesis by regulating the status of EMT and autophagy (28). Sun et al (29) demonstrated that Tripartite Motif Containing 29 facilitated the EMT of CRC via the activation of the Wnt/β-catenin signaling pathway.…”