PRL3 promotes cell invasion and proliferation by down-regulation of Csk leading to Src activation

Fubo Liang, Jiao Liang, Wei Qing Wang, Jin Peng Sun, Eshwar Udho, Zhong-Yin Zhang

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

Phosphatase of regenerating liver 3 (PRL3) is overexpressed in a variety of tumors, and high levels of PRL3 expression are associated with tumorigenesis and metastasis. Consistent with an oncogenic role for PRL3, we show that ectopic PRL3 expression promotes cell proliferation and invasion. However, little is known about the molecular basis for PRL3 function. Obtaining this knowledge is vital for understanding PRL3-mediated disease processes and for the development of novel anticancer therapies targeted to PRL3. Here we report that up-regulation of PRL3 activates the Src kinase, which initiates a number of signal pathways culminating in the phosphorylation of ERK1/2, STAT3, and p130Cas. The activation of these pathways likely contributes to the increased cell growth and motility of PRL3 cells. We provide evidence that PRL3 induces Src activation through down-regulation of Csk, a negative regulator of Src. Importantly, Src activation and Csk down-regulation are also observed in colon cancer cells expressing a higher level of PRL3. Thus, we have revealed a biochemical mechanism for the PRL3-mediated cell invasion and proliferation in which elevated PRL3 expression causes a reduction in Csk level, leading to Src activation.

Original languageEnglish
Pages (from-to)5413-5419
Number of pages7
JournalJournal of Biological Chemistry
Volume282
Issue number8
DOIs
StatePublished - Feb 23 2007

Fingerprint

Phosphoric Monoester Hydrolases
Liver
Down-Regulation
Chemical activation
Cell Proliferation
Phosphorylation
src-Family Kinases
Cell proliferation
Cell growth
Colonic Neoplasms
Cell Movement
Tumors
Signal Transduction
Carcinogenesis
Up-Regulation
Cells
Neoplasm Metastasis

ASJC Scopus subject areas

  • Biochemistry

Cite this

PRL3 promotes cell invasion and proliferation by down-regulation of Csk leading to Src activation. / Liang, Fubo; Liang, Jiao; Wang, Wei Qing; Sun, Jin Peng; Udho, Eshwar; Zhang, Zhong-Yin.

In: Journal of Biological Chemistry, Vol. 282, No. 8, 23.02.2007, p. 5413-5419.

Research output: Contribution to journalArticle

Liang, Fubo ; Liang, Jiao ; Wang, Wei Qing ; Sun, Jin Peng ; Udho, Eshwar ; Zhang, Zhong-Yin. / PRL3 promotes cell invasion and proliferation by down-regulation of Csk leading to Src activation. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 8. pp. 5413-5419.
@article{6acbac09436f48d88e36f5dc3a295dbb,
title = "PRL3 promotes cell invasion and proliferation by down-regulation of Csk leading to Src activation",
abstract = "Phosphatase of regenerating liver 3 (PRL3) is overexpressed in a variety of tumors, and high levels of PRL3 expression are associated with tumorigenesis and metastasis. Consistent with an oncogenic role for PRL3, we show that ectopic PRL3 expression promotes cell proliferation and invasion. However, little is known about the molecular basis for PRL3 function. Obtaining this knowledge is vital for understanding PRL3-mediated disease processes and for the development of novel anticancer therapies targeted to PRL3. Here we report that up-regulation of PRL3 activates the Src kinase, which initiates a number of signal pathways culminating in the phosphorylation of ERK1/2, STAT3, and p130Cas. The activation of these pathways likely contributes to the increased cell growth and motility of PRL3 cells. We provide evidence that PRL3 induces Src activation through down-regulation of Csk, a negative regulator of Src. Importantly, Src activation and Csk down-regulation are also observed in colon cancer cells expressing a higher level of PRL3. Thus, we have revealed a biochemical mechanism for the PRL3-mediated cell invasion and proliferation in which elevated PRL3 expression causes a reduction in Csk level, leading to Src activation.",
author = "Fubo Liang and Jiao Liang and Wang, {Wei Qing} and Sun, {Jin Peng} and Eshwar Udho and Zhong-Yin Zhang",
year = "2007",
month = "2",
day = "23",
doi = "10.1074/jbc.M608940200",
language = "English",
volume = "282",
pages = "5413--5419",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "8",

}

TY - JOUR

T1 - PRL3 promotes cell invasion and proliferation by down-regulation of Csk leading to Src activation

AU - Liang, Fubo

AU - Liang, Jiao

AU - Wang, Wei Qing

AU - Sun, Jin Peng

AU - Udho, Eshwar

AU - Zhang, Zhong-Yin

PY - 2007/2/23

Y1 - 2007/2/23

N2 - Phosphatase of regenerating liver 3 (PRL3) is overexpressed in a variety of tumors, and high levels of PRL3 expression are associated with tumorigenesis and metastasis. Consistent with an oncogenic role for PRL3, we show that ectopic PRL3 expression promotes cell proliferation and invasion. However, little is known about the molecular basis for PRL3 function. Obtaining this knowledge is vital for understanding PRL3-mediated disease processes and for the development of novel anticancer therapies targeted to PRL3. Here we report that up-regulation of PRL3 activates the Src kinase, which initiates a number of signal pathways culminating in the phosphorylation of ERK1/2, STAT3, and p130Cas. The activation of these pathways likely contributes to the increased cell growth and motility of PRL3 cells. We provide evidence that PRL3 induces Src activation through down-regulation of Csk, a negative regulator of Src. Importantly, Src activation and Csk down-regulation are also observed in colon cancer cells expressing a higher level of PRL3. Thus, we have revealed a biochemical mechanism for the PRL3-mediated cell invasion and proliferation in which elevated PRL3 expression causes a reduction in Csk level, leading to Src activation.

AB - Phosphatase of regenerating liver 3 (PRL3) is overexpressed in a variety of tumors, and high levels of PRL3 expression are associated with tumorigenesis and metastasis. Consistent with an oncogenic role for PRL3, we show that ectopic PRL3 expression promotes cell proliferation and invasion. However, little is known about the molecular basis for PRL3 function. Obtaining this knowledge is vital for understanding PRL3-mediated disease processes and for the development of novel anticancer therapies targeted to PRL3. Here we report that up-regulation of PRL3 activates the Src kinase, which initiates a number of signal pathways culminating in the phosphorylation of ERK1/2, STAT3, and p130Cas. The activation of these pathways likely contributes to the increased cell growth and motility of PRL3 cells. We provide evidence that PRL3 induces Src activation through down-regulation of Csk, a negative regulator of Src. Importantly, Src activation and Csk down-regulation are also observed in colon cancer cells expressing a higher level of PRL3. Thus, we have revealed a biochemical mechanism for the PRL3-mediated cell invasion and proliferation in which elevated PRL3 expression causes a reduction in Csk level, leading to Src activation.

UR - http://www.scopus.com/inward/record.url?scp=34247119239&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247119239&partnerID=8YFLogxK

U2 - 10.1074/jbc.M608940200

DO - 10.1074/jbc.M608940200

M3 - Article

C2 - 17192274

AN - SCOPUS:34247119239

VL - 282

SP - 5413

EP - 5419

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 8

ER -