Cdx1 and Cdx2 Function as tumor suppressors

Alexa Hryniuk, Stephanie Grainger, Joanne G.A. Savory, David Lohnes

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

In humans, colorectal cancer is often initiated through APC loss of function, which leads to crypt hyperplasia and polyposis driven by unrestricted canonical Wnt signaling. Such polyps typically arise in the colorectal region and are at risk of transforming to invasive adenocarcinomas.Althoughcolorectal cancer is the thirdmost common cause of cancer-related death worldwide, the processes impacting initiation, transformation, and invasion are incompletely understood. Murine APCMin/+ mutants are often used to model colorectal cancers; however, they develop nonmetastatic tumors confined largely to the small intestine and are thus not entirely representative of the human disease. APCMin/+ alleles can collaborate with mutations impacting other pathways to recapitulate some aspects of human colorectal cancer. To this end, we assessed APCMin/+-induced polyposis following somatic loss of the homeodomain transcription factor Cdx2, alone or with a Cdx1 null allele, in the adult gastrointestinal tract. APCMin/+-Cdx2 mutants recapitulated several aspects of human colorectal cancer, including an invasive phenotype. Notably, the concomitant loss of Cdx1 led to a significant increase in the incidence of tumors in the distal colon, relative to APCMin/+-Cdx2 offspring, demonstrating a previously unrecognized role for this transcription factor in colorectal tumorigenesis. These findings underscore previously unrecognized roles for Cdx members in intestinal tumorigenesis.

Original languageEnglish (US)
Pages (from-to)33343-33354
Number of pages12
JournalJournal of Biological Chemistry
Volume289
Issue number48
DOIs
StatePublished - Nov 28 2014

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Tumors
Colorectal Neoplasms
Transcription Factors
Neoplasms
Carcinogenesis
Alleles
Polyps
Small Intestine
Hyperplasia
Gastrointestinal Tract
Colon
Adenocarcinoma
Phenotype
Mutation
Incidence

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Cdx1 and Cdx2 Function as tumor suppressors. / Hryniuk, Alexa; Grainger, Stephanie; Savory, Joanne G.A.; Lohnes, David.

In: Journal of Biological Chemistry, Vol. 289, No. 48, 28.11.2014, p. 33343-33354.

Research output: Contribution to journalArticle

Hryniuk, A, Grainger, S, Savory, JGA & Lohnes, D 2014, 'Cdx1 and Cdx2 Function as tumor suppressors', Journal of Biological Chemistry, vol. 289, no. 48, pp. 33343-33354. https://doi.org/10.1074/jbc.M114.583823
Hryniuk, Alexa ; Grainger, Stephanie ; Savory, Joanne G.A. ; Lohnes, David. / Cdx1 and Cdx2 Function as tumor suppressors. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 48. pp. 33343-33354.
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