• Open Access

LAPTM4B-35, a novel tetratransmembrane protein and its PPRP motif play critical roles in proliferation and metastatic potential of hepatocellular carcinoma cells

Authors

  • Xinrong Liu,

    1. Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing, China
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    • 3

      These authors contributed equally to this study.

    • 4

      Present address: Department of Radiology, University of Massachusetts Medical School, Worcester, MA, USA.

  • Fuxia Xiong,

    1. Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing, China
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    • 3

      These authors contributed equally to this study.

  • Xuanhui Wei,

    1. Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing, China
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    • 3

      These authors contributed equally to this study.

  • Hua Yang,

    1. Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing, China
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  • Rouli Zhou

    Corresponding author
    1. Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing, China
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To whom correspondence should be addressed. E-mail: rlzhou@bjmu.edu.cn

Abstract

Lysosomal protein transmembrane 4 beta (LAPTM4B) was originally identified as a hepatocellular carcinoma (HCC)-associated gene. This gene and its protein product LAPTM4B-35, are both overexpressed in a variety of human cancers. However, its specific role in cell transformation and malignancy has remained elusive. In the present study we investigated the effects of LAPTM4B-35 overexpression on the malignant phenotypic features in the HLE cell line. Our data show that overexpression of LAPTM4B-35 promotes cell proliferation, exogenous growth-stimulating factor-independent and anchorage-independent growth, and enhances metastatic potential, including promotion of both cell migration and invasion. Study of the underlying mechanisms demonstrated alterations of molecular events involved in these processes, which included upregulation of proliferation-promoting transcription factors such as c-Myc, c-Jun, and c-Fos, and cell cycle-promoting proteins such as cyclin D1 and cyclin E. In addition, mutagenesis study showed that the PPRP motif in the N-terminal region of LAPTM4B-35 plays a critical role in promoting proliferation, migration, and invasion, as well as in the upregulation of the oncoproteins noted above. These data offer insight into the mechanism by which this novel tetratransmembrane protein contributes to the pathogenesis of liver cancer, and suggest that it may be a potential target for cancer therapy. (Cancer Sci 2009)

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