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Tumour Biol. 2016 Jun;37(6):8305-15. doi: 10.1007/s13277-015-4704-4. Epub 2016 Jan 4.

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

Zhang H1,2, Li Z1,2, Chu B1,2, Zhang F1,2, Zhang Y1,2, Ke F1,2, Chen Y1,2, Xu Y1,2, Liu S1,2, Zhao S1,2, Liang H1,2, Weng M1,2, Wu X1,2, Li M1,2, Wu W1,2, Quan Z1,2, Liu Y1,2, Zhang Y1,2, Gong W3,4.

Author information

1
Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai, 200092, China.
2
The Institute of Biliary Disease Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai, 200092, China.
3
Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai, 200092, China. 13651819806@163.com.
4
The Institute of Biliary Disease Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai, 200092, China. 13651819806@163.com.

Abstract

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 (Pā€‰<ā€‰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.

KEYWORDS:

Apoptosis; Cell invasion; Cell migration; Cell proliferation; LASP-1CCA; Prognosis

PMID:
26729195
DOI:
10.1007/s13277-015-4704-4
[Indexed for MEDLINE]

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