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Type of publication: Journal Article
Type of document: Full Paper

Year: 2018

Authors: Crnčec, I; Modak, M; Gordziel, C; Svinka, J; Scharf, I; Moritsch, S; Pathria, P; Schlederer, M; Kenner, L; Timelthaler, G; Müller, M; Strobl, B; Casanova, E; Bayer, E; Mohr, T; Stöckl, J; Friedrich, K; Eferl, R

Title: STAT1 is a sex-specific tumor suppressor in colitis-associated colorectal cancer.

Source: Mol Oncol 12(4): 514-528.



Authors Vetmeduni Vienna:

Kenner Lukas
Müller Mathias
Strobl Birgit

Vetmed Research Units
Institute of Pathology, Pathology of Laboratory Animals
Institute of Animal Breeding and Genetics, Unit of Molecular Genetics


Abstract:
The interferon-inducible transcription factor STAT1 is a tumor suppressor in various malignancies. We investigated sex-specific STAT1 functions in colitis and colitis-associated colorectal cancer (CRC) using mice with specific STAT1 deletion in intestinal epithelial cells (STAT1∆IEC ). Male but not female STAT1∆IEC mice were more resistant to DSS-induced colitis than sex-matched STAT1flox/flox controls and displayed reduced intraepithelial infiltration of CD8+ TCRαβ+ granzyme B+ T cells. Moreover, DSS treatment failed to induce expression of T-cell-attracting chemokines in intestinal epithelial cells of male but not of female STAT1∆IEC mice. Application of the AOM-DSS protocol for induction of colitis-associated CRC resulted in increased intestinal tumor load in male but not in female STAT1∆IEC mice. A sex-specific stratification of human CRC patients corroborated the data obtained in mice and revealed that reduced tumor cell-intrinsic nuclear STAT1 protein expression is a poor prognostic factor in men but not in women. These data demonstrate that epithelial STAT1 is a male-specific tumor suppressor in CRC of mice and humans.© 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Keywords Pubmed: Animals
CD8-Positive T-Lymphocytesmetabolismpathology
Chemokinesbiosynthesis
Colitischemically inducedmetabolismpathology
Colorectal Neoplasmschemically inducedgeneticsmetabolismpathology
Dextran Sulfatetoxicity
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Mice
Mice, Transgenic
Receptors, Antigen, T-Cell, alpha-betametabolism
STAT1 Transcription Factorgeneticsmetabolism
Sex Characteristics
Tumor Suppressor Proteinsgeneticsmetabolism

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