| RRC ID |
63497
|
| 著者 |
Ando M, Kawazu M, Ueno T, Koinuma D, Ando K, Koya J, Kataoka K, Yasuda T, Yamaguchi H, Fukumura K, Yamato A, Soda M, Sai E, Yamashita Y, Asakage T, Miyazaki Y, Kurokawa M, Miyazono K, Nimer SD, Yamasoba T, Mano H.
|
| タイトル |
Mutational Landscape and Antiproliferative Functions of ELF Transcription Factors in Human Cancer.
|
| ジャーナル |
Cancer Res
|
| Abstract |
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.
|
| 巻・号 |
76(7)
|
| ページ |
1814-24
|
| 公開日 |
2016-4-1
|
| DOI |
10.1158/0008-5472.CAN-14-3816
|
| PII |
0008-5472.CAN-14-3816
|
| PMID |
26921333
|
| MeSH |
DNA-Binding Proteins / genetics*
Humans
Mutation
Neoplasms / genetics*
Transcription Factors / genetics*
|
| IF |
9.727
|
| リソース情報 |
| ヒト・動物細胞 |
T3M-1 Cl-10(RCB1017) |
