Oncotarget

Research Papers:

Paxillin promotes colorectal tumor invasion and poor patient outcomes via ERK-mediated stabilization of Bcl-2 protein by phosphorylation at Serine 87

Chi-Chou Huang, De-Wei Wu, Po-Lin Lin and Huei Lee _

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Oncotarget. 2015; 6:8698-8708. https://doi.org/10.18632/oncotarget.3537

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Abstract

Chi-Chou Huang1,2,*, De-Wei Wu3,*, Po-Lin Lin4 and Huei Lee3

1 School of Medicine, Chung Shan Medical University, Taichung, Taiwan

2 Department of Surgery, Division of Colon and Rectum, Chung Shan Medical University Hospital, Taichung, Taiwan

3 Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical University, Taipei, Taiwan

4 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

* These authors contributed equally to this work

Correspondence to:

Huei Lee, email:

Keywords: paxillin, Bcl-2 phosphorylation, prognosis, colorectal cancer

Received: December 08, 2014 Accepted: February 10, 2015 Published: March 12, 2015

Abstract

Stabilization of Bcl-2 protein by paxillin (PXN)-mediated ERK activation was recently reported to cause an unfavorable response to 5-Fluorouracil-based chemotherapy. Here, we present evidence from cell and animal models to demonstrate that stabilization of Bcl-2 protein by phosphorylation at Serine 87 (pBcl-2-S87) via PXN-mediated ERK activation is responsible for cancer cell invasiveness and occurs via upregulation of MMP2 expression. Immunostainings of 190 tumors resected from colorectal cancer patients indicated that PXN expression was positively correlated with Bcl-2, pBcl-2-S87, and MMP2 expression. A positive correlation of pBcl-2-S87 with Bcl-2 and MMP2 was also observed in this study population. Patients with high PXN, Bcl-2, pBcl-2-S87, and MMP2 had poor overall survival (OS) and shorter relapse free survival (RFS). In conclusion, PXN promotes Bcl-2 phosphorylation at Serine 87 via PXN-mediated ERK activation, and its stabilization associated with increased tumor formation efficacy in mice and poor patient outcome in colorectal cancer patients.


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