Details

Autor(en) / Beteiligte

• Collins, Ross J.
• Morgan, Liam D.
• Owen, Sioned
• Ruge, Fiona
• Jiang, Wen G.
• Sanders, Andrew J.

Titel

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

Ist Teil von

• International journal of cancer, 2018-11, Vol.143 (10), p.2537-2550

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• 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. What's new? There is growing evidence that EPLIN is a tumor suppressor molecule in several human cancers. The underlying mechanisms, however, remain unclear. Here, the authors provide functional evidence that EPLIN is a negative regulator of prostate cancer and acts as a tumor suppressor to impede metastatic traits. They document downregulation of EPLIN in clinical prostate cancer and a potential mechanistic link between EPLIN and proto‐oncogene tyrosine‐protein kinase (Src)/Focal adhesion kinase (FAK) signaling. This study provides insights into molecular associations which drive the regulatory actions of EPLIN, and establishes a broader picture of the signaling cascades coordinating cellular functions in prostate cancer.