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Upregulated LASP-1 correlates with a malignant phenotype and its potential therapeutic role in human cholangiocarcinoma
Journal article   Peer reviewed

Upregulated LASP-1 correlates with a malignant phenotype and its potential therapeutic role in human cholangiocarcinoma

Hongchen Zhang, Zhizhen Li, Bingfeng Chu, Fei Zhang, Yijian Zhang, Fayong Ke, Yuanyuan Chen, Yi Xu, Shibo Liu, Shuai Zhao, …
Tumor biology, v 37(6), pp 8305-8315
Jun 2016
PMID: 26729195

Abstract

Adaptor Proteins, Signal Transducing - metabolism Animals Apoptosis Bile Duct Neoplasms - genetics Bile Duct Neoplasms - metabolism Bile Duct Neoplasms - pathology Blotting, Western Carcinogenesis - genetics Carcinogenesis - metabolism Cell Line, Tumor Cell Movement - genetics Cell Proliferation - genetics Cholangiocarcinoma - genetics Cholangiocarcinoma - metabolism Cholangiocarcinoma - pathology Cytoskeletal Proteins - metabolism Female Gene Expression Regulation, Neoplastic - physiology Humans Immunohistochemistry LIM Domain Proteins - metabolism Male Mice Neoplasm Invasiveness - genetics Phenotype Prognosis Real-Time Polymerase Chain Reaction RNA, Small Interfering Up-Regulation
LIM and SH3 protein 1 (LASP-1) is demonstrated to play a key role in occurrence and development of tumors. However, the expression and function of LASP-1 in cholangiocarcinoma (CCA) remain largely unexplored. This study aimed to investigate the effect of regulated LASP-1 expression on migration, invasion, proliferation, and apoptosis of CCA cells and on tumorigenesis in vivo, and to examine clinico-oncological correlates of LASP-1 expression. Expression of LASP-1 by immunohistochemistry was evaluated in CCA tissue samples. HCCC-9810 and RBE cells were transfected with the LASP-1 small interfering RNA (siRNA), and the effect of knocking down LASP-1 gene expression on cell migration, invasion, proliferation, and apoptosis were examined by wound healing, transwell assays, CCK-8 assays, colony formation, and flow cytometry assays, respectively. Xenograft tumor model was used to validate the effect of downregulated LASP-1 in vivo. Our results demonstrated that LASP-1 was over-expressed in CCA tissues, positively correlating with larger tumors, poor histological differentiation, lymph node metastasis, advanced TNM stage, and poor prognosis in CCA patients (P < 0.05). Downregulation of LASP-1 in HCCC-9810 and RBE cell lines significantly increased cell apoptosis and suppressed cell migration, invasion, and proliferation in vitro and tumorigenesis in vivo. Our results indicate that LASP-1 may essentially involve in the metastasis and growth of CCA and clinical significance of LASP-1 may reside in function as a biomarker to predict prognosis and as a promising therapeutic strategy for CCA patients by the inhibition of LASP-1 expression.

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Web of Science research areas
Oncology
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