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

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Tumor Biology

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 (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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Acknowledgments

This study was supported by the Introductory Funding project from Shanghai Science and Technology Bureau (124119a0600) to WG and Science and Technology funding project of Shanghai Jiao Tong University, School of Medicine (13xj22003) to BFC.

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    Authors and Affiliations

    1. Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai, 200092, China

      Hongchen Zhang, Zhizhen Li, Bingfeng Chu, Fei Zhang, Yijian Zhang, Fayong Ke, Yuanyuan Chen, Yi Xu, Shibo Liu, Shuai Zhao, Haibin Liang, Mingzhe Weng, Xiangsong Wu, Maolan Li, Wenguang Wu, Zhiwei Quan, Yingbin Liu, Yong Zhang & Wei Gong

    2. The Institute of Biliary Disease Research, School of Medicine, Shanghai Jiao Tong University, 1665 Kongjiang Road, Shanghai, 200092, China

      Hongchen Zhang, Zhizhen Li, Bingfeng Chu, Fei Zhang, Yijian Zhang, Fayong Ke, Yuanyuan Chen, Yi Xu, Shibo Liu, Shuai Zhao, Haibin Liang, Mingzhe Weng, Xiangsong Wu, Maolan Li, Wenguang Wu, Zhiwei Quan, Yingbin Liu, Yong Zhang & Wei Gong

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    1. Hongchen Zhang
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    Corresponding author

    Correspondence to Wei Gong.

    Ethics declarations

    This study was performed with approval of the Ethics Committee of Xinhua Hospital and the ethical guidelines of the Declaration of Helsinki. In addition, written informed consent was obtained from all participants.

    All experimental procedures were approved by the Institutional Animal Care and Use Committee of Shanghai Jiao Tong University (Shanghai, China).

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    Hongchen Zhang, Zhizhen Li and Bingfeng Chu contributed equally to this work.

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    Zhang, H., Li, Z., Chu, B. et al. Upregulated LASP-1 correlates with a malignant phenotype and its potential therapeutic role in human cholangiocarcinoma. Tumor Biol. 37, 8305–8315 (2016). https://doi.org/10.1007/s13277-015-4704-4

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    • DOI: https://doi.org/10.1007/s13277-015-4704-4

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