A role for p53 in the regulation of extracellular matrix metalloproteinase inducer in human cancer cells

Hua Zhu, Brad Evans, Peter O'Neill, Xingcong Ren, Zude Xu, William N. Hait, Jin-Ming Yang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

EMMPRIN, a transmembrane glycoprotein known to promote survival, invasion and metastasis of tumor cells through multiple pathways and mechanisms, has been found to be overexpressed in various types of cancer cells. Here we report that loss of the function of p53, a tumor suppressor protein that is mutated in approximately 50% of human cancers, contributes to the upregulation of EMMPRIN protein. We observed an inverse association between the activity of p53 and the level of EMMPRIN protein in several cancer cell lines. We further demonstrated that p53 is able to negatively regulate EMMPRIN protein, but downregulation of EMMPRIN by p53 is independent of repression of the EMMPRIN transcription. Furthermore, downregulation of EMMPRIN by p53 can be rescued by chloroquine, a lysosome inhibitor, but not by MG132, a proteasome inhibitor, suggesting an involvement of the lysosomal pathway in the p53-regulated degradation of EMMPRIN. Downregulation of EMMPRIN by p53 leads to a decrease in the activity of MMP-9 and an inhibition of tumor cell invasion. Our study suggests that the upregulation of EMMPRIN seen in many cancers can be attributed to, at least in part, the dysfunction of p53 and thus provides new evidence for the roles of p53 in tumor development and progression.

Original languageEnglish (US)
Pages (from-to)1722-1728
Number of pages7
JournalCancer Biology and Therapy
Volume8
Issue number18
DOIs
StatePublished - Sep 15 2009

Fingerprint

CD147 Antigens
Neoplasms
Down-Regulation
Up-Regulation
Tumor Suppressor Protein p53
Proteins
Proteasome Inhibitors
Chloroquine
Lysosomes
Matrix Metalloproteinases
Glycoproteins
Neoplasm Metastasis
Cell Line
Survival

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

Cite this

Zhu, Hua ; Evans, Brad ; O'Neill, Peter ; Ren, Xingcong ; Xu, Zude ; Hait, William N. ; Yang, Jin-Ming. / A role for p53 in the regulation of extracellular matrix metalloproteinase inducer in human cancer cells. In: Cancer Biology and Therapy. 2009 ; Vol. 8, No. 18. pp. 1722-1728.
@article{de25e2b19c8749938f9bb1f7df9dafae,
title = "A role for p53 in the regulation of extracellular matrix metalloproteinase inducer in human cancer cells",
abstract = "EMMPRIN, a transmembrane glycoprotein known to promote survival, invasion and metastasis of tumor cells through multiple pathways and mechanisms, has been found to be overexpressed in various types of cancer cells. Here we report that loss of the function of p53, a tumor suppressor protein that is mutated in approximately 50{\%} of human cancers, contributes to the upregulation of EMMPRIN protein. We observed an inverse association between the activity of p53 and the level of EMMPRIN protein in several cancer cell lines. We further demonstrated that p53 is able to negatively regulate EMMPRIN protein, but downregulation of EMMPRIN by p53 is independent of repression of the EMMPRIN transcription. Furthermore, downregulation of EMMPRIN by p53 can be rescued by chloroquine, a lysosome inhibitor, but not by MG132, a proteasome inhibitor, suggesting an involvement of the lysosomal pathway in the p53-regulated degradation of EMMPRIN. Downregulation of EMMPRIN by p53 leads to a decrease in the activity of MMP-9 and an inhibition of tumor cell invasion. Our study suggests that the upregulation of EMMPRIN seen in many cancers can be attributed to, at least in part, the dysfunction of p53 and thus provides new evidence for the roles of p53 in tumor development and progression.",
author = "Hua Zhu and Brad Evans and Peter O'Neill and Xingcong Ren and Zude Xu and Hait, {William N.} and Jin-Ming Yang",
year = "2009",
month = "9",
day = "15",
doi = "10.4161/cbt.8.18.9207",
language = "English (US)",
volume = "8",
pages = "1722--1728",
journal = "Cancer Biology and Therapy",
issn = "1538-4047",
publisher = "Landes Bioscience",
number = "18",

}

A role for p53 in the regulation of extracellular matrix metalloproteinase inducer in human cancer cells. / Zhu, Hua; Evans, Brad; O'Neill, Peter; Ren, Xingcong; Xu, Zude; Hait, William N.; Yang, Jin-Ming.

In: Cancer Biology and Therapy, Vol. 8, No. 18, 15.09.2009, p. 1722-1728.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A role for p53 in the regulation of extracellular matrix metalloproteinase inducer in human cancer cells

AU - Zhu, Hua

AU - Evans, Brad

AU - O'Neill, Peter

AU - Ren, Xingcong

AU - Xu, Zude

AU - Hait, William N.

AU - Yang, Jin-Ming

PY - 2009/9/15

Y1 - 2009/9/15

N2 - EMMPRIN, a transmembrane glycoprotein known to promote survival, invasion and metastasis of tumor cells through multiple pathways and mechanisms, has been found to be overexpressed in various types of cancer cells. Here we report that loss of the function of p53, a tumor suppressor protein that is mutated in approximately 50% of human cancers, contributes to the upregulation of EMMPRIN protein. We observed an inverse association between the activity of p53 and the level of EMMPRIN protein in several cancer cell lines. We further demonstrated that p53 is able to negatively regulate EMMPRIN protein, but downregulation of EMMPRIN by p53 is independent of repression of the EMMPRIN transcription. Furthermore, downregulation of EMMPRIN by p53 can be rescued by chloroquine, a lysosome inhibitor, but not by MG132, a proteasome inhibitor, suggesting an involvement of the lysosomal pathway in the p53-regulated degradation of EMMPRIN. Downregulation of EMMPRIN by p53 leads to a decrease in the activity of MMP-9 and an inhibition of tumor cell invasion. Our study suggests that the upregulation of EMMPRIN seen in many cancers can be attributed to, at least in part, the dysfunction of p53 and thus provides new evidence for the roles of p53 in tumor development and progression.

AB - EMMPRIN, a transmembrane glycoprotein known to promote survival, invasion and metastasis of tumor cells through multiple pathways and mechanisms, has been found to be overexpressed in various types of cancer cells. Here we report that loss of the function of p53, a tumor suppressor protein that is mutated in approximately 50% of human cancers, contributes to the upregulation of EMMPRIN protein. We observed an inverse association between the activity of p53 and the level of EMMPRIN protein in several cancer cell lines. We further demonstrated that p53 is able to negatively regulate EMMPRIN protein, but downregulation of EMMPRIN by p53 is independent of repression of the EMMPRIN transcription. Furthermore, downregulation of EMMPRIN by p53 can be rescued by chloroquine, a lysosome inhibitor, but not by MG132, a proteasome inhibitor, suggesting an involvement of the lysosomal pathway in the p53-regulated degradation of EMMPRIN. Downregulation of EMMPRIN by p53 leads to a decrease in the activity of MMP-9 and an inhibition of tumor cell invasion. Our study suggests that the upregulation of EMMPRIN seen in many cancers can be attributed to, at least in part, the dysfunction of p53 and thus provides new evidence for the roles of p53 in tumor development and progression.

UR - http://www.scopus.com/inward/record.url?scp=73249152867&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73249152867&partnerID=8YFLogxK

U2 - 10.4161/cbt.8.18.9207

DO - 10.4161/cbt.8.18.9207

M3 - Article

C2 - 19597352

AN - SCOPUS:73249152867

VL - 8

SP - 1722

EP - 1728

JO - Cancer Biology and Therapy

JF - Cancer Biology and Therapy

SN - 1538-4047

IS - 18

ER -