title: STAT1 drives tumor progression in serous papillary endometrial cancer.
abstract: 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.
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Budiman
authors.initials: B
authors.lastname: Kharma
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan. babatsu@kuhp.kyoto-u.ac.jp.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Baba
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Noriomi
authors.initials: N
authors.lastname: Matsumura
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Kang
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Junzo
authors.initials: J
authors.lastname: Hamanishi
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Murakami
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: McConechy
authors.affiliation: Genetic Pathology Evaluation Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: Leung
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hosoe
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yoshioka
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Murphy
authors.affiliation: Department of Obstetrics and Gynecology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Mandai
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. Genetic Pathology Evaluation Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
authors.forename: David G
authors.initials: DG
authors.lastname: Hunstman
authors.affiliation: Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D018283:Cystadenocarcinoma, Papillary / Q000473:pathology*; D018284:Cystadenocarcinoma, Serous / Q000473:pathology*; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000209:etiology / Q000401:mortality / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D016259:Genes, myc; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D011379:Prognosis; D050794:STAT1 Transcription Factor / Q000032:analysis / Q000502:physiology*
chemical_list: D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D007371:Interferon-gamma