| RRC ID |
45009
|
| 著者 |
Watanabe A, Suzuki H, Yokobori T, Tsukagoshi M, Altan B, Kubo N, Suzuki S, Araki K, Wada S, Kashiwabara K, Hosouchi Y, Kuwano H.
|
| タイトル |
Stathmin1 regulates p27 expression, proliferation and drug resistance, resulting in poor clinical prognosis in cholangiocarcinoma.
|
| ジャーナル |
Cancer Sci
|
| Abstract |
Patients with extrahepatic cholangiocarcinoma (EHCC) have a poor prognosis; postoperative survival depends on cancer progression and therapeutic resistance. The mechanism of EHCC progression needs to be clarified to identify ways to improve disease prognosis. Stathmin1 (STMN1) is a major cytosolic phosphoprotein that regulates microtubule dynamics and is associated with malignant phenotypes and chemoresistance in various cancers. Recently, STMN1 was reported to interact with p27, an inhibitor of cyclin-dependent kinase complexes. Eighty EHCC cases were studied using immunohistochemistry and clinical pathology to determine the correlation between STMN1 and p27 expression; RNA interference to analyze the function of STMN1 in an EHCC cell line was also used. Cytoplasmic STMN1 expression correlated with venous invasion (P = 0.0021) and nuclear p27 underexpression (P = 0.0011). Patients in the high-STMN1-expression group were associated with shorter recurrence-free survival and overall survival than those in the low-expression group. An in vitro protein-binding assay revealed that cytoplasmic STMN1 bound to p27 in the cytoplasm, but not in the nucleus of EHCC cells. Moreover, p27 accumulated in EHCC cells after STMN1 suppression. STMN1 knockdown inhibited proliferation and increased the sensitivity of EHCC cells to paclitaxel. STMN1 contributes to a poor prognosis and cancer progression in EHCC patients. Understanding the regulation of p27 by STMN1 could provide new insights for overcoming therapeutic resistance in EHCC.
|
| 巻・号 |
105(6)
|
| ページ |
690-6
|
| 公開日 |
2014-6-1
|
| DOI |
10.1111/cas.12417
|
| PMID |
24708177
|
| PMC |
PMC4317896
|
| MeSH |
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Phytogenic / pharmacology
Bile Duct Neoplasms / drug therapy*
Bile Duct Neoplasms / mortality
Bile Duct Neoplasms / surgery
Bile Ducts, Intrahepatic / drug effects
Bile Ducts, Intrahepatic / surgery
Biomarkers, Tumor / genetics
Cell Line, Tumor
Cell Proliferation
Cholangiocarcinoma / drug therapy*
Cholangiocarcinoma / mortality
Cholangiocarcinoma / surgery
Cyclin-Dependent Kinase Inhibitor p27 / biosynthesis
Cyclin-Dependent Kinase Inhibitor p27 / genetics
Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
Disease Progression
Drug Resistance, Neoplasm
Female
Gene Expression
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Male
Middle Aged
Paclitaxel / pharmacology
Protein Binding
RNA Interference
RNA, Small Interfering
Stathmin / genetics
Stathmin / metabolism*
Treatment Outcome
|
| IF |
4.966
|
| 引用数 |
29
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
HuCCT1(RCB1960) |
