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, Huei Lee

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)8698-8708
Number of pages11
JournalOncotarget
Volume6
Issue number11
Publication statusPublished - 2015

Fingerprint

Paxillin
Serine
Colorectal Neoplasms
Phosphorylation
Proteins
Neoplasms
Survival
Fluorouracil
Up-Regulation
Animal Models
Recurrence
Drug Therapy
Population

Keywords

  • Bcl-2 phosphorylation
  • Colorectal cancer
  • Paxillin
  • Prognosis

ASJC Scopus subject areas

  • Oncology

Cite this

Paxillin promotes colorectal tumor invasion and poor patient outcomes via ERK-mediated stabilization of Bcl-2 protein by phosphorylation at Serine 87. / Huang, Chi Chou; Wu, De Wei; Lin, Po Lin; Lee, Huei.

In: Oncotarget, Vol. 6, No. 11, 2015, p. 8698-8708.

Research output: Contribution to journalArticle

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