Mechanistic insights of epithelial protein lost in neoplasm in prostate cancer metastasis

Abstract

EPLIN is frequently downregulated or lost in various cancers. The purpose of this study was to evaluate the importance of EPLIN in prostate cancer progression, with particular focus on the mechanistic implications to elucidate EPLIN's tumor suppressive function in cancer. EPLIN expression was evaluated in prostate cancer cell lines and tissues. PC-3 and LNCaP EPLINα overexpression models were generated through transfection with EPLINα sequence and EPLIN knockdown was achieved using shRNA in CA-HPV-10 cells. Functional assays were performed to evaluate cellular characteristics and potential mechanisms were evaluated using a protein microarray, and validated using western blot analysis. EPLIN expression was reduced in clinical prostate cancer sections, including hyperplasia (p ≤ 0.001) and adenocarcinoma (p = 0.005), when compared to normal prostate tissue. EPLINα overexpression reduced cell growth, migration and invasion, and influenced transcript, protein and phosphoprotein expression of paxillin, FAK and Src. EPLIN knockdown increased the invasive and migratory nature of CA-HPV-10 cells and also induced changes to FAK and Src total and/or phospho expression. Functional characterization of cellular migration and invasion in addition to FAK and Src inhibition demonstrated differential effects between control and EPLINα overexpression and EPLIN knockdown cell lines. This study highlights that EPLIN expression in prostate cancer is able to influence several aspects of cancer cell characteristics, including cell growth, migration and invasion. The mechanism of the tumor suppressive action of EPLIN remains to be fully elucidated; and this study proposes a role for EPLIN's ability to regulate the aggressive characteristics of prostate cancer cells partially through regulating FAK/Src signaling.

LUZP1 and the tumor suppressor EPLIN modulate actin stability to restrict primary cilia formation

“…On the other hand, EPLIN loss of expression has been associated with cancer. This has been shown to affect cancer cell adhesion and migration and increase metastatic potential (Collins et al, 2018;Jiang et al, 2008;Liu et al, 2012;Sanders et al, 2010;Zhang et al, 2011). Like LUZP1, EPLIN had never been implicated in cilia biology.…”

EPLIN Expression in Gastric Cancer and Impact on Prognosis and Chemoresistance

“…EPLIN is widely expressed in normal epithelial cells but frequently lost in cancer cells and tissues [6][7][8]18,19].…”

“…Additionally, EPLIN engages in cell-cell adherence junctions by linking the cadherin-β-catenin-α-catenin-EPLIN-F-actin complex. It is also suggested to interact with paxillin [11,[16][17][18] and plays an indispensable role in stabilising apical-basal polarity in epithelial cells [9]. Previous studies revealed that EPLIN negatively correlates with epithelial mesenchymal transition (EMT), invasiveness, metastasis, poor prognosis, mortality and therapeutic resistance in human tumours such as prostate, breast, ovarian and oesophageal cancers [6,7,9,19,20], and that epidermal growth factor (EGF) could cause protein phosphorylation and turnover of EPLIN through an extracellular signal-regulated kinase (ERK) signal pathway to influence EMT [21].…”

Overexpression of E74-Like Factor 5 (ELF5) Inhibits Migration and Invasion of Ovarian Cancer Cells

“…Invasive ability in vitro is important in determining tumor metastasis potential [30]. Wound-healing assay and Transwell chamber analysis data showed that the metastasis ability of ovarian cancer SKOV3 cells was significantly decreased after transfection of the ELF5 gene, indicating that the ELF5 gene has a significant inhibitory effect on host invasion and motility of ovarian cancer SKOV3 cells.…”