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Molecular and Cellular Pathobiology

STAT1 Drives Tumor Progression in Serous Papillary Endometrial Cancer

Budiman Kharma, Tsukasa Baba, Noriomi Matsumura, Hyun Sook Kang, Junzo Hamanishi, Ryusuke Murakami, Melissa M. McConechy, Samuel Leung, Ken Yamaguchi, Yuko Hosoe, Yumiko Yoshioka, Susan K. Murphy, Masaki Mandai, David G. Hunstman and Ikuo Konishi
Budiman Kharma
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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Tsukasa Baba
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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  • For correspondence: babatsu@kuhp.kyoto-u.ac.jp
Noriomi Matsumura
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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Hyun Sook Kang
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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Junzo Hamanishi
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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Ryusuke Murakami
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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Melissa M. McConechy
Department of Pathology and Laboratory Medicine, University of British Columbia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
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Samuel Leung
Genetic Pathology Evaluation Centre, Vancouver General Hospital, Vancouver, British Columbia, Canada.
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Ken Yamaguchi
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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Yuko Hosoe
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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Yumiko Yoshioka
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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Susan K. Murphy
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina.
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Masaki Mandai
Department of Obstetrics and Gynecology, Kinki University Faculty of Medicine, Osaka, Japan.
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David G. Hunstman
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.
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Ikuo Konishi
Department of Gynecology and Obstetrics, Kyoto University Graduate School of Medicine, Kyoto, Japan.
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DOI: 10.1158/0008-5472.CAN-14-0847
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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. Cancer Res; 74(22); 1–12. ©2014 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received April 2, 2014.
  • Revision received August 7, 2014.
  • Accepted August 31, 2014.
  • ©2014 American Association for Cancer Research.
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Published OnlineFirst November 4, 2014
doi: 10.1158/0008-5472.CAN-14-0847

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STAT1 Drives Tumor Progression in Serous Papillary Endometrial Cancer
Budiman Kharma, Tsukasa Baba, Noriomi Matsumura, Hyun Sook Kang, Junzo Hamanishi, Ryusuke Murakami, Melissa M. McConechy, Samuel Leung, Ken Yamaguchi, Yuko Hosoe, Yumiko Yoshioka, Susan K. Murphy, Masaki Mandai, David G. Hunstman and Ikuo Konishi
Cancer Res November 4 2014 DOI: 10.1158/0008-5472.CAN-14-0847

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STAT1 Drives Tumor Progression in Serous Papillary Endometrial Cancer
Budiman Kharma, Tsukasa Baba, Noriomi Matsumura, Hyun Sook Kang, Junzo Hamanishi, Ryusuke Murakami, Melissa M. McConechy, Samuel Leung, Ken Yamaguchi, Yuko Hosoe, Yumiko Yoshioka, Susan K. Murphy, Masaki Mandai, David G. Hunstman and Ikuo Konishi
Cancer Res November 4 2014 DOI: 10.1158/0008-5472.CAN-14-0847
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