| RRC ID |
65877
|
| 著者 |
Tsukagoshi M, Araki K, Yokobori T, Altan B, Suzuki H, Kubo N, Watanabe A, Ishii N, Hosouchi Y, Nishiyama M, Shirabe K, Kuwano H.
|
| タイトル |
Overexpression of karyopherin-α2 in cholangiocarcinoma correlates with poor prognosis and gemcitabine sensitivity via nuclear translocation of DNA repair proteins.
|
| ジャーナル |
Oncotarget
|
| Abstract |
Cholangiocarcinoma is a highly malignant tumor, and the development of new therapeutic strategies is critical. Karyopherin-α2 (KPNA2) functions as an adaptor that mediates nucleocytoplasmic transport. Specifically, KPNA2 transports one of the important DNA repair machineries, the MRE11-RAD50-NBS1 (MRN) complex, to the nucleus. In this study, we clarified the significance of KPNA2 in cholangiocarcinoma. KPNA2 expression evaluated by immunohistochemical analysis was common in malignant tissue but rare in adjacent noncancerous tissues. KPNA2 overexpression was significantly correlated with poor prognosis and was an independent prognostic factor after surgery. In patients with cholangiocarcinoma who received gemcitabine after surgery, KPNA2 overexpression tended to be a prognostic indicator of poor overall survival. In KPNA2-depleted cholangiocarcinoma cells, proliferation was significantly decreased and gemcitabine sensitivity was enhanced in vitro and in vivo. Expression of KPNA2 and the MRN complex displayed colocalization in the nucleus. In addition, nuclear localization of the MRN complex was regulated by KPNA2 in vitro. These results suggest that KPNA2 expression may be a useful prognostic and predictive marker of gemcitabine sensitivity and survival. The regulation of KPNA2 expression may be a new therapeutic strategy for cholangiocarcinoma.
|
| 巻・号 |
8(26)
|
| ページ |
42159-42172
|
| 公開日 |
2017-6-27
|
| DOI |
10.18632/oncotarget.15020
|
| PII |
15020
|
| PMID |
28178675
|
| PMC |
PMC5522057
|
| MeSH |
Aged
Antineoplastic Agents / pharmacology
Bile Duct Neoplasms / drug therapy
Bile Duct Neoplasms / genetics*
Bile Duct Neoplasms / mortality*
Bile Duct Neoplasms / pathology
Biomarkers, Tumor
Cell Line, Tumor
Cell Proliferation / genetics
Cholangiocarcinoma / drug therapy
Cholangiocarcinoma / genetics*
Cholangiocarcinoma / mortality*
Cholangiocarcinoma / pathology
DNA Repair*
Deoxycytidine / analogs & derivatives
Deoxycytidine / pharmacology
Drug Resistance, Neoplasm / genetics*
Female
Gemcitabine
Gene Expression
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Male
Middle Aged
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Staging
Prognosis
Protein Transport
RNA Interference
Tumor Burden
alpha Karyopherins / genetics*
alpha Karyopherins / metabolism
|
| IF |
5.168
|
| リソース情報 |
| ヒト・動物細胞 |
TFK-1(RCB2537)
HuCCT1(RCB1960) |
