Open AccessLAPTM4B‐35, a novel tetratransmembrane protein and its PPRP motif play critical roles in proliferation and metastatic potential of hepatocellular carcinoma cells
Author(s) -
Liu Xinrong,
Xiong Fuxia,
Wei Xuanhui,
Yang Hua,
Zhou Rouli
Publication year - 2009
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01346.x
Subject(s) - cyclin d1 , cancer research , cell growth , downregulation and upregulation , biology , cell cycle , carcinogenesis , transcription factor , cell , cancer , microbiology and biotechnology , gene , genetics
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)