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.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
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 Rdoi
10.1002/1878-0261.12178subject
Has Abstractpub_date
2018-04-01 00:00:00pages
514-528issue
4eissn
1574-7891issn
1878-0261journal_volume
12pub_type
杂志文章abstract::The presence of circulating tumor cells (CTCs) in the blood of ovarian cancer patients was shown to correlate with decreased overall survival, whereby CTCs with epithelial-mesenchymal-transition (EMT) or stem-like traits are supposed to be involved in metastatic progression and recurrence. Thus, investigating the tran...
journal_title:Molecular oncology
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