STAT1 drives tumor progression in serous papillary endometrial cancer.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kharma, B; Baba, T; Matsumura, N; Kang, HS; Hamanishi, J; Murakami, R; McConechy, MM; Leung, S; Yamaguchi, K; Hosoe, Y; Yoshioka, Y; Murphy, SK; Mandai, M; Hunstman, DG; Konishi, I

Published Date

  • November 2014

Published In

Volume / Issue

  • 74 / 22

Start / End Page

  • 6519 - 6530

PubMed ID

  • 25267067

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

International Standard Serial Number (ISSN)

  • 0008-5472

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.can-14-0847

Language

  • eng