| RRC ID |
63505
|
| 著者 |
Hamada J, Shoda K, Masuda K, Fujita Y, Naruto T, Kohmoto T, Miyakami Y, Watanabe M, Kudo Y, Fujiwara H, Ichikawa D, Otsuji E, Imoto I.
|
| タイトル |
Tumor-promoting function and prognostic significance of the RNA-binding protein T-cell intracellular antigen-1 in esophageal squamous cell carcinoma.
|
| ジャーナル |
Oncotarget
|
| Abstract |
T-cell intracellular antigen-1 (TIA1) is an RNA-binding protein involved in many regulatory aspects of mRNA metabolism. Here, we report previously unknown tumor-promoting activity of TIA1, which seems to be associated with its isoform-specific molecular distribution and regulation of a set of cancer-related transcripts, in esophageal squamous cell carcinoma (ESCC). Immunohistochemical overexpression of TIA1 ectopically localized in the cytoplasm of tumor cells was an independent prognosticator for worse overall survival in a cohort of 143 ESCC patients. Knockdown of TIA1 inhibited proliferation of ESCC cells. By exogenously introducing each of two major isoforms, TIA1a and TIA1b, only TIA1a, which was localized to both the nucleus and cytoplasm, promoted anchorage-dependent and anchorage-independent ESCC cell proliferation. Ribonucleoprotein immunoprecipitation, followed by microarray analysis or massive-parallel sequencing, identified a set of TIA1-binding mRNAs, including SKP2 and CCNA2. TIA1 increased SKP2 and CCNA2 protein levels through the suppression of mRNA decay and translational induction, respectively. Our findings uncover a novel oncogenic function of TIA1 in esophageal tumorigenesis, and implicate its use as a marker for prognostic evaluation and as a therapeutic target in ESCC.
|
| 巻・号 |
7(13)
|
| ページ |
17111-28
|
| 公開日 |
2016-3-29
|
| DOI |
10.18632/oncotarget.7937
|
| PII |
7937
|
| PMID |
26958940
|
| PMC |
PMC4941375
|
| MeSH |
Adult
Aged
Biomarkers, Tumor / analysis
Carcinogenesis / metabolism*
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / mortality
Carcinoma, Squamous Cell / pathology*
Cell Proliferation / physiology
Esophageal Neoplasms / metabolism
Esophageal Neoplasms / mortality
Esophageal Neoplasms / pathology*
Esophageal Squamous Cell Carcinoma
Female
Gene Expression Regulation, Neoplastic / physiology
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Prognosis
Proportional Hazards Models
T-Cell Intracellular Antigen-1 / analysis
T-Cell Intracellular Antigen-1 / metabolism*
|
| IF |
5.168
|
| リソース情報 |
| ヒト・動物細胞 |
TE-9(RCB1988)
TE-15(RCB1951)
TE-6(RCB1950)
TE-14(RCB2101)
TE-11(RCB2100)
TE-10(RCB2099)
TE-8(RCB2098)
TE-4(RCB2097)
TE-1(RCB1894)
TE-5(RCB1949) |
