A Calon

A Hryniuk

A Spandidos

AA Bhat

AK Olsen

AK San Roman

C Tyner

CT Ong

CY Lin

D Hnisz

D Huang

DB Stairs

DG Silberg

F Escaffit

H Itoh

H Ji

H Kataoka

H Li

H Sakamoto

IJ Hidalgo

J Olsen

J Yang

JB Zheng

JK Wang

JR Turner

JT Troelsen

K List

K Turksen

K Wang

KU Sales

LK Vogel

LT Costa da

M Boyd

M Coskun

M Kawaguchi

M Saxena

MD Oberst

MG Kim

MP Verzi

MS Buzza

P Dalerba

P Kosa

R Pinto

S He

S Hoshiko

S Netzel-Arnett

S Satake

S Satomi

S Simmini

S Xin

SY Chun

T Hinoi

T Sakaguchi

T Takeuchi

TM Antalis

TT Nguyen

W Dou

W Komaki

Y Ogata

English

Crossref

Intestinal regulation of suppression of tumorigenicity 14 (ST14) and serine peptidase inhibitor, Kunitz type -1 (SPINT1) by transcription factor CDX2

The type II membrane-anchored serine protease, matriptase, encoded by suppression of tumorgenicity-14 (ST14) regulates the integrity of the intestinal epithelial barrier in concert with its inhibitor, HAI-1 encoded by serine peptidase inhibitor, Kunitz type -1 (SPINT1). The balance of the protease/inhibitor gene expression ratio is vital in preventing the oncogenic potential of matriptase. The intestinal cell lineage is regulated by a transcriptional regulatory network where the tumor suppressor, Caudal homeobox 2 (CDX2) is considered to be an intestinal master transcription factor. In this study, we show that CDX2 has a dual function in regulating both ST14 and SPINT1, gene expression in intestinal cells. We find that CDX2 is not required for the basal ST14 and SPINT1 gene expression; however changes in CDX2 expression affects the ST14/SPINT1 mRNA ratio. Exploring CDX2 ChIP-seq data from intestinal cell lines, we identified genomic CDX2-enriched enhancer elements for both ST14 and SPINT1, which regulate their corresponding gene promoter activity. We show that CDX2 displays both repressive and enhancing regulatory abilities in a cell specific manner. Together, these data reveal new insight into transcriptional mechanisms controlling the intestinal matriptase/inhibitor balance.The type II membrane-anchored serine protease, matriptase, encoded by suppression of tumorgenicity-14 (ST14) regulates the integrity of the intestinal epithelial barrier in concert with its inhibitor, HAI-1 encoded by serine peptidase inhibitor, Kunitz type -1 (SPINT1). The balance of the protease/inhibitor gene expression ratio is vital in preventing the oncogenic potential of matriptase. The intestinal cell lineage is regulated by a transcriptional regulatory network where the tumor suppressor, Caudal homeobox 2 (CDX2) is considered to be an intestinal master transcription factor. In this study, we show that CDX2 has a dual function in regulating both ST14 and SPINT1, gene expression in intestinal cells. We find that CDX2 is not required for the basal ST14 and SPINT1 gene expression; however changes in CDX2 expression affects the ST14/SPINT1 mRNA ratio. Exploring CDX2 ChIP-seq data from intestinal cell lines, we identified genomic CDX2-enriched enhancer elements for both ST14 and SPINT1, which regulate their corresponding gene promoter activity. We show that CDX2 displays both repressive and enhancing regulatory abilities in a cell specific manner. Together, these data reveal new insight into transcriptional mechanisms controlling the intestinal matriptase/inhibitor balance

Danielsen, Erik Thomas

Olsen, Anders Krüger

Coskun, Mehmet

Nonboe, Annika W.

Larsen, Sylvester

Dahlgaard, Katja

Bennett, Eric Paul

Mitchelmore, Cathy

Vogel, Lotte Katrine

Troelsen, Jesper

Roskilde Universitet

Intestinal regulation of suppression of tumorigenicity 14 (ST14) and serine peptidase inhibitor, Kunitz type -1 (SPINT1) by transcription factor CDX2.

The type II membrane-anchored serine protease, matriptase, encoded by suppression of tumorgenicity-14 (ST14) regulates the integrity of the intestinal epithelial barrier in concert with its inhibitor, HAI-1 encoded by serine peptidase inhibitor, Kunitz type -1 (SPINT1). The balance of the protease/inhibitor gene expression ratio is vital in preventing the oncogenic potential of matriptase. The intestinal cell lineage is regulated by a transcriptional regulatory network where the tumor suppressor, Caudal homeobox 2 (CDX2) is considered to be an intestinal master transcription factor. In this study, we show that CDX2 has a dual function in regulating both ST14 and SPINT1, gene expression in intestinal cells. We find that CDX2 is not required for the basal ST14 and SPINT1 gene expression; however changes in CDX2 expression affects the ST14/SPINT1 mRNA ratio. Exploring CDX2 ChIP-seq data from intestinal cell lines, we identified genomic CDX2-enriched enhancer elements for both ST14 and SPINT1, which regulate their corresponding gene promoter activity. We show that CDX2 displays both repressive and enhancing regulatory abilities in a cell specific manner. Together, these data reveal new insight into transcriptional mechanisms controlling the intestinal matriptase/inhibitor balance.</p

Danielsen, E. Thomas

Troelsen, Jesper Thorvald

Copenhagen University Research Information System

Intestinal regulation of <i>suppression of tumorigenicity</i> 14 (ST14) and <i>serine peptidase inhibitor, Kunitz type -1 (SPINT1)</i> by transcription factor CDX2

https://curis.ku.dk/ws/files/203668509/Intestinal_regulation_of_suppression_of_tumorigenicity_14_ST14_and_serine_peptidase_inhibitor_Kunitz_type_1_SPINT1_by_transcription_factor_CDX2.pdf

Intestinal regulation of suppression of tumorigenicity 14 (ST14) and serine peptidase inhibitor, Kunitz type -1 (SPINT1) by transcription factor CDX2.

Abstract

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Roskilde Universitet

Copenhagen University Research Information System