Molecular oncology, 2018-04, Vol.12 (4), p.514-528
2018
Details
- Autor(en) / Beteiligte
- Titel
- STAT1 is a sex‐specific tumor suppressor in colitis‐associated colorectal cancer
- Ist Teil von
- Molecular oncology, 2018-04, Vol.12 (4), p.514-528
- Ort / Verlag
- United States: John Wiley & Sons, Inc
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- Wiley-Blackwell Journals
- Beschreibungen/Notizen
- 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. The identity of sex‐specific molecular factors in cancer formation and progression remains scarce. We found that the interferon‐inducible transcription factor STAT1 acts as a male‐specific tumor suppressor in colorectal cancer of mice. Moreover, enhanced STAT1 protein expression in tumor cells of human colorectal cancer biopsies is a male‐specific factor for good patient prognosis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1574-7891eISSN: 1878-0261DOI: 10.1002/1878-0261.12178Titel-ID: cdi_doaj_primary_oai_doaj_org_article_470ce83f7ffc4801a6ede8c87a159f05
- Format
- –
- Schlagworte
- Animals, Cancer, CD8 antigen, CD8+ T cells, CD8-Positive T-Lymphocytes - metabolism, CD8-Positive T-Lymphocytes - pathology, Chemokines, Chemokines - biosynthesis, Clonal deletion, Colitis, Colitis - chemically induced, Colitis - metabolism, Colitis - pathology, Colorectal cancer, Colorectal carcinoma, Colorectal Neoplasms - chemically induced, Colorectal Neoplasms - genetics, Colorectal Neoplasms - metabolism, Colorectal Neoplasms - pathology, Dextran Sulfate - toxicity, Drinking water, Epithelial cells, Ethylenediaminetetraacetic acid, Experiments, Female, Flow cytometry, gender, Gene Expression Regulation, Neoplastic, Genetic aspects, Granzyme B, Health aspects, Humans, Immunoglobulins, Inflammatory bowel disease, Interferon, Intestine, Laboratories, Lymphocytes, Lymphocytes T, Male, Medical prognosis, Metastases, Mice, Mice, Transgenic, Penicillin, Receptors, Antigen, T-Cell, alpha-beta - metabolism, Rodents, Sex, Sex Characteristics, Sex differences, STAT1, Stat1 protein, STAT1 Transcription Factor - genetics, STAT1 Transcription Factor - metabolism, Tumor suppressor genes, Tumor Suppressor Proteins - genetics, Tumor Suppressor Proteins - metabolism, Tumors, Ulcers, Women, Womens health