title: Ganoderiol A-enriched extract suppresses migration and adhesion of MDA-MB-231 cells by inhibiting FAK-SRC-paxillin cascade pathway.
abstract: 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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Guo-Sheng
authors.initials: GS
authors.lastname: Wu
authors.forename: Yue-Lin
authors.initials: YL
authors.lastname: Song
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Yin
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Guo
authors.forename: Sheng-Peng
authors.initials: SP
authors.lastname: Wang
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Zhao
authors.forename: Xiu-Ping
authors.initials: XP
authors.lastname: Chen
authors.forename: Qing-Wen
authors.initials: QW
authors.lastname: Zhang
authors.forename: Jin-Jian
authors.initials: JJ
authors.lastname: Lu
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D006801:Humans; D051419:Paxillin / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D011485:Protein Binding; D015398:Signal Transduction / Q000187:drug effects*; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000199:Actins; D051419:Paxillin; D011134:Polysaccharides; C047406:ganoderan A; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D020741:rho GTP-Binding Proteins