Mutational Landscape and Antiproliferative Functions of ELF Transcription Factors in Human Cancer
-
- Mizuo Ando
- 1Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Masahito Kawazu
- 3Department of Medical Genomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Toshihide Ueno
- 1Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Daizo Koinuma
- 4Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Koji Ando
- 5Department of Hematology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
-
- Junji Koya
- 6Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Keisuke Kataoka
- 6Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Takahiko Yasuda
- 1Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Hiroyuki Yamaguchi
- 1Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Kazutaka Fukumura
- 1Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Azusa Yamato
- 1Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Manabu Soda
- 1Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Eirin Sai
- 3Department of Medical Genomics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Yoshihiro Yamashita
- 1Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Takahiro Asakage
- 2Department of Otolaryngology and Head and Neck Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Yasushi Miyazaki
- 5Department of Hematology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
-
- Mineo Kurokawa
- 6Department of Hematology and Oncology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Kohei Miyazono
- 4Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Stephen D. Nimer
- 7Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida.
-
- Tatsuya Yamasoba
- 2Department of Otolaryngology and Head and Neck Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
-
- Hiroyuki Mano
- 1Department of Cellular Signaling, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
書誌事項
- 公開日
- 2016-03-31
- 資源種別
- journal article
- DOI
-
- 10.1158/0008-5472.can-14-3816
- 公開者
- American Association for Cancer Research (AACR)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>ELF4 (also known as MEF) is a member of the ETS family of transcription factors. An oncogenic role for ELF4 has been demonstrated in hematopoietic malignancies, but its function in epithelial tumors remains unclear. Here, we show that ELF4 can function as a tumor suppressor and is somatically inactivated in a wide range of human tumors. We identified a missense mutation affecting the transactivation potential of ELF4 in oral squamous cell carcinoma cells. Restoration of the transactivation activity through introduction of wild-type ELF4 significantly inhibited cell proliferation in vitro and tumor xenograft growth. Furthermore, we found that ELF1 and ELF2, closely related transcription factors to ELF4, also exerted antiproliferative effects in multiple cancer cell lines. Mutations in ELF1 and ELF2, as in ELF4, were widespread across human cancers, but were almost all mutually exclusive. Moreover, chromatin immunoprecipitation coupled with high-throughput sequencing revealed ELF4-binding sites in genomic regions adjacent to genes related to cell-cycle regulation and apoptosis. Finally, we provide mechanistic evidence that the antiproliferative effects of ELF4 were mediated through the induction of HRK, an activator of apoptosis, and DLX3, an inhibitor of cell growth. Collectively, our findings reveal a novel subtype of human cancer characterized by inactivating mutations in the ELF subfamily of proteins, and warrant further investigation of the specific settings where ELF restoration may be therapeutically beneficial. Cancer Res; 76(7); 1814–24. ©2016 AACR.</jats:p>
収録刊行物
-
- Cancer Research
-
Cancer Research 76 (7), 1814-1824, 2016-03-31
American Association for Cancer Research (AACR)
