STAT1 drives tumor progression in serous papillary endometrial cancer

Recent studies of the interferon-induced transcription factor STAT1 have associated its dysregulation with poor prognosis in some cancers, but its mechanistic contributions are not well defined. In this study, we report that the STAT1 pathway is constitutively upregulated in type II endometrial canc...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2014-11, Vol.74 (22), p.6519-6530
Main Authors: Kharma, Budiman, Baba, Tsukasa, Matsumura, Noriomi, Kang, Hyun Sook, Hamanishi, Junzo, Murakami, Ryusuke, McConechy, Melissa M, Leung, Samuel, Yamaguchi, Ken, Hosoe, Yuko, Yoshioka, Yumiko, Murphy, Susan K, Mandai, Masaki, Hunstman, David G, Konishi, Ikuo
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Cystadenocarcinoma, Papillary - pathology
Cystadenocarcinoma, Serous - pathology
Disease Progression
Endometrial Neoplasms - etiology
Endometrial Neoplasms - mortality
Endometrial Neoplasms - pathology
Female
Gene Expression Profiling
Genes, myc
Humans
Interferon-gamma - physiology
Mice
Prognosis
STAT1 Transcription Factor - analysis
STAT1 Transcription Factor - physiology
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Summary:Recent studies of the interferon-induced transcription factor STAT1 have associated its dysregulation with poor prognosis in some cancers, but its mechanistic contributions are not well defined. In this study, we report that the STAT1 pathway is constitutively upregulated in type II endometrial cancers. STAT1 pathway alteration was especially prominent in serous papillary endometrial cancers (SPEC) that are refractive to therapy. Our results defined a "SPEC signature" as a molecular definition of its malignant features and poor prognosis. Specifically, we found that STAT1 regulated MYC as well as ICAM1, PD-L1, and SMAD7, as well as the capacity for proliferation, adhesion, migration, invasion, and in vivo tumorigenecity in cells with a high SPEC signature. Together, our results define STAT1 as a driver oncogene in SPEC that modulates disease progression. We propose that STAT1 functions as a prosurvival gene in SPEC, in a manner important to tumor progression, and that STAT1 may be a novel target for molecular therapy in this disease.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-14-0847