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Overexpression of PITPNM3 promotes hepatocellular carcinoma cell metastasis

  • Article
  • Cell Biology
  • Published:
Chinese Science Bulletin

Abstract

A previous study indicated that C–C chemokine (C–C motif) ligand 18 (CCL18) is capable of inducing tumor cell invasion and metastasis by interacting with receptor membrane-associated phosphatidylinositol transfer protein 3 (PITPNM3) in breast cancer cells. The present study aims to investigate the correlation between the PITPNM3 expression and metastasis in hepatocellular carcinoma (HCC). Real-time quantitative polymerase chain reaction and Western blot were performed to detect the expression pattern of PITPNM3 in patient samples and HCC cell lines. Wound-healing and transwell chamber assays were performed to assess the migration and invasiveness of HCC cells, and the activation of the signaling protein downstream of PITPNM3 was also detected by Western blot and immunofluorescence. The results revealed that PITPNM3 was upregulated in HCC tissue compared to matched normal liver tissue. Silencing the expression of PITPNM3 by specific siRNAs markedly attenuated the invasive and metastatic abilities of HCC cells, whereas the upregulation of PITPNM3 significantly increased HCC cell mobility. Furthermore, inhibiting the expression of PITPNM3 suppressed the activation of Pyk2, FAK, and Src, while overexpression of PITPNM3 enhanced the phosphorylation of FAK and Src in HCC cells. Besides, suppression of Pyk2 can also impair the clustering of integrin. These results imply that PITPNM3 is a vital determinant of HCC migration and invasion.

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Acknowledgments

This work was supported by the National Key Basic Research Program of China (2010CB912800, 2011CB504203); the National Natural Science Foundation of China (81102022, 81230060, 81261140373, 81000917, and 81372819); the Foundation for the Young Teachers in the Higher Education Institutions of China (20110171120082); the National S&T Major Special Project on New Drug Innovation of China (2011ZX09102-010-02); the Science Foundation of Guangdong Province (S2012030006287); the Translational Medicine Public Platform of Guangdong Province (4202037) and the Foundation of the Ministry of Education of China (20120171110075); funding from Sun Yat-Sen University (13ykzd14) and the grant [2013]163 from Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology.

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Authors and Affiliations

  1. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China

    Chonghua He, Shicheng Su, Fei Chen, Di Huang, Fang Zheng, Wei Huang, Jianing Chen, Xiuying Cui, Qiang Liu, Erwei Song, Herui Yao & Yujie Liu

  2. Department of Breast Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China

    Chonghua He, Shicheng Su, Fei Chen, Di Huang, Wei Huang, Jianing Chen, Qiang Liu, Erwei Song & Yujie Liu

  3. Department of Oncology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China

    Herui Yao

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  1. Chonghua He
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  2. Shicheng Su
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Correspondence to Herui Yao or Yujie Liu.

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Chonghua He and Shicheng Su contributed equally to this work.

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He, C., Su, S., Chen, F. et al. Overexpression of PITPNM3 promotes hepatocellular carcinoma cell metastasis. Chin. Sci. Bull. 59, 1326–1333 (2014). https://doi.org/10.1007/s11434-014-0183-z

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  • DOI: https://doi.org/10.1007/s11434-014-0183-z

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