Stathmin decreases cholangiocarcinoma cell line sensitivity to staurosporine-triggered apoptosis via the induction of ERK and Akt signaling.
Cholangiocarcinoma is a rare, but highly fatal malignancy. However, the intrinsic mechanism involved in its tumorigenesis remains obscure. An urgent need remains for a promising target for cholangiocarcinoma biological therapies. Based on comparative proteomical technologies, we found 253 and 231 different spots in gallbladder tumor cell lines and cholangiocarcinoma cell lines, respectively, relative to non-malignant cells. Using Mass Spectrometry (MS) and database searching, we chose seven differentially expressed proteins. High Stathmin expression was found in both cholangiocarcinoma and gallbladder carcinoma cells. Stathmin expression was validated using immunohistochemistry and western blot in cholangiocarcinoma tissue samples and peritumoral tissue. It was further revealed that high Stathmin expression was associated with the repression of staurosporine-induced apoptosis in the cholangiocarcinoma cell. Moreover, we found that Stathmin promoted cancer cell proliferation and inhibited its apoptosis through protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) signaling. Integrin, β1 appears to serve as a partner of Stathmin induction of ERK and Akt signaling by inhibiting apoptosis in the cholangiocarcinoma cell. Understanding the regulation of anti-apoptosis effect by Stathmin might provide new insight into how to overcome therapeutic resistance in cholangiocarcinoma.
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Yueqi
Y
Wang
Department of General Surgery, Subei People's Hospital, Yangzhou, Jiangsu Province, China.
Zhihui
Z
Gao
Department of General Surgery, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
Dexiang
D
Zhang
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Xiaobo
X
Bo
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Yaojie
Y
Wang
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Jiwen
J
Wang
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Sheng
S
Shen
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Han
H
Liu
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Tao
T
Suo
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Hongtao
H
Pan
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Zhilong
Z
Ai
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Houbao
H
Liu
D017209:Apoptosis / Q000187:drug effects*; D001650:Bile Duct Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018281:Cholangiocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019012:Integrin beta1; D050777:Stathmin; D051057:Proto-Oncogene Proteins c-akt; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D019311:Staurosporine
Stathmin; cholangiocarcinoma; integrin β1; proteomics; staurosporine