Stathmin1 regulates p27 expression, proliferation and drug resistance, resulting in poor clinical prognosis in cholangiocarcinoma

• DOI: 10.1111/cas.12417
• Publication Date: 2014-04-08T09:06:23Z
• Authors: Akira Watanabe; Hideki Suzuki; Takehiko Yokobori; Mariko Tsukagoshi; Bolag Altan; Norio Kubo; Shigemasa Suzuki; Kenichiro Araki; Satoshi Wada; Kenji Kashiwabara; Yasuo Hosouchi; Hiroyuki Kuwano
• Keywords: Adult; Male; Gene Expression; Cholangiocarcinoma; 03 medical and health sciences; 0302 clinical medicine; Cell Line, Tumor; Biomarkers, Tumor; Humans; Aged; Cell Proliferation; Aged, 80 and over; Original Articles; Middle Aged; Antineoplastic Agents, Phytogenic; Immunohistochemistry; 3. Good health; Gene Expression Regulation, Neoplastic; Bile Ducts, Intrahepatic; Bile Duct Neoplasms; Drug Resistance, Neoplasm; Disease Progression; Female; Cyclin-Dependent Kinase Inhibitor p27

Patients with extrahepatic cholangiocarcinoma (EHCC) have a poor prognosis; postoperative survival depends on cancer progression and therapeutic resistance. The mechanism of EHCC needs to be clarified identify ways improve disease prognosis. Stathmin1 (STMN1) is major cytosolic phosphoprotein that regulates microtubule dynamics associated malignant phenotypes chemoresistance in various cancers. Recently, STMN1 was reported interact p27, an inhibitor cyclin-dependent kinase complexes. Eighty cases were studied using immunohistochemistry clinical pathology determine the correlation between p27 expression; RNA interference analyze function cell line also used. Cytoplasmic expression correlated venous invasion (P = 0.0021) nuclear underexpression 0.0011). high-STMN1-expression group shorter recurrence-free overall than those low-expression group. An vitro protein-binding assay revealed cytoplasmic bound cytoplasm, but not nucleus cells. Moreover, accumulated cells after suppression. knockdown inhibited proliferation increased sensitivity paclitaxel. contributes prognosis patients. Understanding regulation by could provide new insights for overcoming resistance EHCC.