Open AccessLKB1 is required for adiponectin-mediated modulation of AMPK–S6K axis and inhibition of migration and invasion of breast cancer cells
Author(s) -
La Tonia Taliaferro-Smith,
Arumugam Nagalingam,
Diansheng Zhong,
Weibo Zhou,
Neeraj K. Saxena,
Dipali Sharma
Publication year - 2009
Publication title -
oncogene
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.395
H-Index - 342
eISSN - 1476-5594
pISSN - 0950-9232
DOI - 10.1038/onc.2009.129
Subject(s) - ampk , adiponectin , biology , cancer research , p70 s6 kinase 1 , endocrinology , carcinogenesis , downregulation and upregulation , breast cancer , medicine , gene knockdown , protein kinase a , cancer , phosphorylation , microbiology and biotechnology , protein kinase b , insulin resistance , cell culture , insulin , gene , biochemistry , genetics
Adiponectin is widely known as an adipocytokine with therapeutic potential for its markedly protective function in the pathogenesis of obesity-related disorders, metabolic syndrome, systemic insulin resistance, cardiovascular disease and more recently carcinogenesis. In the present study, we show that adiponectin inhibits adhesion, invasion and migration of breast cancer cells. Further analysis of the underlying molecular mechanisms revealed that adiponectin treatment increased AMP-activated protein kinase (AMPK) phosphorylation and activity as evident by increased phosphorylation of downstream target of AMPK, acetyl-coenzyme A carboxylase and inhibition of p70S6 kinase (S6K). Intriguingly, we discovered that adiponectin treatment increases the expression of tumor suppressor gene LKB1 in breast cancer cells. Overexpression of LKB1 in breast cancer cells further increased adiponectin-mediated phosphorylation of AMPK. Using isogenic LKB1 knockdown cell line pair, we found that LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and more importantly, inhibition of adhesion, migration and invasion of breast cancer cells. Taken together these data present a novel mechanism involving specific upregulation of tumor suppressor gene LKB1 by which adiponectin inhibits adhesion, invasion and migration of breast cancer cells. Our findings indicate the possibility of using adiponectin analogues to inhibit invasion and migration of breast cancer cells.