GATA6 promotes colon cancer cell invasion by regulating urokinase plasminogen activator gene expression

Narasimhaswamy S. Belaguli, Muhammad Aftab, Mohammed Rigi, Mao Zhang, Daniel Albo, David H. Berger

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

GATA6 is a zinc finger transcription factor expressed in the colorectal epithelium. We have examined the expression of GATA6 in colon cancers and investigated the mechanisms by which GATA6 regulates colon cancer cell invasion. GATA6 was overexpressed in colorectal polyps and primary and metastatic tumors. GATA6 was strongly expressed in both the nuclear and cytoplasmic compartments of the colon cancer cells. GATA6 expression was upregulated in invasive HT29 and KM12L4 cells compared with the parental HT29 and KM12 cells and positively correlated with urokinase-type plasminogen activator (uPA) gene expression. Small interfering RNA (siRNA) knockdown of GATA6 resulted in reduced uPA gene expression and cell invasion. GATA6 bound to the uPA gene regulatory sequences in vivo and activated uPA promoter activity in vitro. uPA promoter deletion analysis indicated that the promoter proximal Sp1 sites were required for GATA6 activation of the uPA promoter. Accordingly, GATA6 physically associated with Sp1 and siRNA knockdown of Sp1 decreased GATA6 activation of the uPA promoter activity suggesting that Sp1 recruits GATA6 to the uPA promoter and mediates GATA6 induced activation of the uPA promoter activity. On the basis of our results, we conclude that GATA6 is an important regulator of uPA gene expression, and the dysregulated expression of GATA6 contributes to colorectal tumorigenesis and tumor invasion.

Original languageEnglish (US)
Pages (from-to)856-865
Number of pages10
JournalNeoplasia
Volume12
Issue number11
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Fingerprint

Plasminogen Activators
Urokinase-Type Plasminogen Activator
Colonic Neoplasms
Gene Expression
HT29 Cells
Small Interfering RNA
Zinc Fingers
Regulator Genes
Polyps
Colorectal Neoplasms
Carcinogenesis
Transcription Factors
Epithelium

ASJC Scopus subject areas

  • Cancer Research

Cite this

GATA6 promotes colon cancer cell invasion by regulating urokinase plasminogen activator gene expression. / Belaguli, Narasimhaswamy S.; Aftab, Muhammad; Rigi, Mohammed; Zhang, Mao; Albo, Daniel; Berger, David H.

In: Neoplasia, Vol. 12, No. 11, 01.01.2010, p. 856-865.

Research output: Contribution to journalArticle

Belaguli, Narasimhaswamy S. ; Aftab, Muhammad ; Rigi, Mohammed ; Zhang, Mao ; Albo, Daniel ; Berger, David H. / GATA6 promotes colon cancer cell invasion by regulating urokinase plasminogen activator gene expression. In: Neoplasia. 2010 ; Vol. 12, No. 11. pp. 856-865.
@article{c9ff52a629b04c2b8cb7fd91b576b61c,
title = "GATA6 promotes colon cancer cell invasion by regulating urokinase plasminogen activator gene expression",
abstract = "GATA6 is a zinc finger transcription factor expressed in the colorectal epithelium. We have examined the expression of GATA6 in colon cancers and investigated the mechanisms by which GATA6 regulates colon cancer cell invasion. GATA6 was overexpressed in colorectal polyps and primary and metastatic tumors. GATA6 was strongly expressed in both the nuclear and cytoplasmic compartments of the colon cancer cells. GATA6 expression was upregulated in invasive HT29 and KM12L4 cells compared with the parental HT29 and KM12 cells and positively correlated with urokinase-type plasminogen activator (uPA) gene expression. Small interfering RNA (siRNA) knockdown of GATA6 resulted in reduced uPA gene expression and cell invasion. GATA6 bound to the uPA gene regulatory sequences in vivo and activated uPA promoter activity in vitro. uPA promoter deletion analysis indicated that the promoter proximal Sp1 sites were required for GATA6 activation of the uPA promoter. Accordingly, GATA6 physically associated with Sp1 and siRNA knockdown of Sp1 decreased GATA6 activation of the uPA promoter activity suggesting that Sp1 recruits GATA6 to the uPA promoter and mediates GATA6 induced activation of the uPA promoter activity. On the basis of our results, we conclude that GATA6 is an important regulator of uPA gene expression, and the dysregulated expression of GATA6 contributes to colorectal tumorigenesis and tumor invasion.",
author = "Belaguli, {Narasimhaswamy S.} and Muhammad Aftab and Mohammed Rigi and Mao Zhang and Daniel Albo and Berger, {David H.}",
year = "2010",
month = "1",
day = "1",
doi = "10.1593/neo.10224",
language = "English (US)",
volume = "12",
pages = "856--865",
journal = "Neoplasia (United States)",
issn = "1522-8002",
publisher = "Elsevier Inc.",
number = "11",

}

TY - JOUR

T1 - GATA6 promotes colon cancer cell invasion by regulating urokinase plasminogen activator gene expression

AU - Belaguli, Narasimhaswamy S.

AU - Aftab, Muhammad

AU - Rigi, Mohammed

AU - Zhang, Mao

AU - Albo, Daniel

AU - Berger, David H.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - GATA6 is a zinc finger transcription factor expressed in the colorectal epithelium. We have examined the expression of GATA6 in colon cancers and investigated the mechanisms by which GATA6 regulates colon cancer cell invasion. GATA6 was overexpressed in colorectal polyps and primary and metastatic tumors. GATA6 was strongly expressed in both the nuclear and cytoplasmic compartments of the colon cancer cells. GATA6 expression was upregulated in invasive HT29 and KM12L4 cells compared with the parental HT29 and KM12 cells and positively correlated with urokinase-type plasminogen activator (uPA) gene expression. Small interfering RNA (siRNA) knockdown of GATA6 resulted in reduced uPA gene expression and cell invasion. GATA6 bound to the uPA gene regulatory sequences in vivo and activated uPA promoter activity in vitro. uPA promoter deletion analysis indicated that the promoter proximal Sp1 sites were required for GATA6 activation of the uPA promoter. Accordingly, GATA6 physically associated with Sp1 and siRNA knockdown of Sp1 decreased GATA6 activation of the uPA promoter activity suggesting that Sp1 recruits GATA6 to the uPA promoter and mediates GATA6 induced activation of the uPA promoter activity. On the basis of our results, we conclude that GATA6 is an important regulator of uPA gene expression, and the dysregulated expression of GATA6 contributes to colorectal tumorigenesis and tumor invasion.

AB - GATA6 is a zinc finger transcription factor expressed in the colorectal epithelium. We have examined the expression of GATA6 in colon cancers and investigated the mechanisms by which GATA6 regulates colon cancer cell invasion. GATA6 was overexpressed in colorectal polyps and primary and metastatic tumors. GATA6 was strongly expressed in both the nuclear and cytoplasmic compartments of the colon cancer cells. GATA6 expression was upregulated in invasive HT29 and KM12L4 cells compared with the parental HT29 and KM12 cells and positively correlated with urokinase-type plasminogen activator (uPA) gene expression. Small interfering RNA (siRNA) knockdown of GATA6 resulted in reduced uPA gene expression and cell invasion. GATA6 bound to the uPA gene regulatory sequences in vivo and activated uPA promoter activity in vitro. uPA promoter deletion analysis indicated that the promoter proximal Sp1 sites were required for GATA6 activation of the uPA promoter. Accordingly, GATA6 physically associated with Sp1 and siRNA knockdown of Sp1 decreased GATA6 activation of the uPA promoter activity suggesting that Sp1 recruits GATA6 to the uPA promoter and mediates GATA6 induced activation of the uPA promoter activity. On the basis of our results, we conclude that GATA6 is an important regulator of uPA gene expression, and the dysregulated expression of GATA6 contributes to colorectal tumorigenesis and tumor invasion.

UR - http://www.scopus.com/inward/record.url?scp=78449260187&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78449260187&partnerID=8YFLogxK

U2 - 10.1593/neo.10224

DO - 10.1593/neo.10224

M3 - Article

VL - 12

SP - 856

EP - 865

JO - Neoplasia (United States)

JF - Neoplasia (United States)

SN - 1522-8002

IS - 11

ER -