Open AccessGanoderiol A-Enriched Extract Suppresses Migration and Adhesion of MDA-MB-231 Cells by Inhibiting FAK-SRC-Paxillin Cascade Pathway
Author(s) -
Guoying Wu,
Yu Song,
Zhiqi Yin,
Jiajie Guo,
Shengpeng Wang,
Wenwen Zhao,
Xiuping Chen,
Qingwen Zhang,
JinJian Lu,
Ying Wang
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0076620
Subject(s) - paxillin , focal adhesion , proto oncogene tyrosine protein kinase src , cdc42 , rhoa , cell migration , cancer research , cell adhesion , rac1 , microbiology and biotechnology , metastasis , cortactin , cancer cell , chemistry , carcinogenesis , adhesion , actin cytoskeleton , biology , actin , cancer , signal transduction , cell , biochemistry , cytoskeleton , genetics , organic chemistry
Cell adhesion, migration and invasion are critical steps for carcinogenesis and cancer metastasis. Ganoderma lucidum , also called Lingzhi in China, is a traditional Chinese medicine, which exhibits anti-proliferation, anti-inflammation and anti-metastasis properties. Herein, GAEE, G. lucidum extract mainly contains ganoderiol A (GA), dihydrogenated GA and GA isomer, was shown to inhibit the abilities of adhesion and migration, while have a slight influence on that of invasion in highly metastatic breast cancer MDA-MB-231 cells at non-toxic doses. Further investigation revealed that GAEE decreased the active forms of focal adhesion kinase (FAK) and disrupted the interaction between FAK and SRC, which lead to deactivating of paxillin. Moreover, GAEE treatment downregulated the expressions of RhoA, Rac1, and Cdc42, and decreased the interaction between neural Wiskott-Aldrich Syndrome protein (N-WASP) and Cdc42, which impair cell migration and actin assembly. To our knowledge, this is the first report to show that G.lucidum triterpenoids could suppress cell migration and adhesion through FAK-SRC-paxillin signaling pathway. Our study also suggests that GAEE may be a potential agent for treatment of breast cancer.