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LRRC4 inhibits the proliferation of human glioma cells by modulating the expression of STMN1 and microtubule polymerization
Author(s) -
Wang Rong,
Wang Zeyou,
Yang Jing,
Liu Xiaoping,
Wang Li,
Guo Xiaofang,
Zeng Fang,
Wu Minghua,
Li Guiyuan
Publication year - 2011
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.23293
Subject(s) - glioma , cell growth , cell cycle , gene knockdown , cyclin d1 , cancer research , microbiology and biotechnology , cell cycle checkpoint , biology , chemistry , cell , apoptosis , biochemistry
LRRC4 is a tumor suppressor of glioma, and it is epigenetically inactivated commonly in glioma. Our previous study has shown that induction of LRRC4 expression inhibits the proliferation of glioma cells. However, little is known about the mechanisms underlying the action of LRRC4 in glioma cells. We employed two‐dimensional fluorescence differential gel electrophoresis (2‐D DIGE) and MALDI –TOF/TOF‐MS/MS to identify 11 differentially expressed proteins, including the significantly down‐regulated STMN1 expression in the LRRC4‐expressing U251 glioma cells. The levels of STMN1 expression appeared to be positively associated with the pathogenic degrees of human glioma. Furthermore, induction of LRRC4 over‐expression inhibited the STMN1 expression and U251 cell proliferation in vitro, and the glioma growth in vivo. In addition, induction of LRRC4 or knockdown of STMN1 expression induced cell cycle arrest in U251 cells, which was associated with modulating the p21, cyclin D1, and cyclin B expression, and the ERK phosphorylation, and inhibiting the CDK5 and cdc2 kinase activities, but increasing the microtubulin polymerization in U251 cells. LRRC4, at least partially by down‐regulating the STMN1expression, acts as a major glioma suppressor, induces cell cycle arrest and modulates the dynamic process of microtubulin, leading to the inhibition of glioma cell proliferation and growth. Potentially, modulation of LRRC4 or STMN1 expression may be useful for design of new therapies for the intervention of glioma. J. Cell. Biochem. 112: 3621–3629, 2011. © 2011 Wiley Periodicals, Inc.