Open AccessDysadherin expression promotes the motility and survival of human breast cancer cells by AKT activation
Author(s) -
Lee YooKyung,
Lee SuYoun,
Park JeongRan,
Kim RanJu,
Kim SooRim,
Roh KyungJin,
Nam JeongSeok
Publication year - 2012
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.1349-7006.2012.02302.x
Subject(s) - protein kinase b , breast cancer , cancer research , motility , metastasis , epithelial–mesenchymal transition , cancer , metastatic breast cancer , gene knockdown , immunohistochemistry , pi3k/akt/mtor pathway , phosphorylation , cancer cell , cell migration , medicine , biology , cell , signal transduction , cell culture , microbiology and biotechnology , genetics
High dysadherin expression has been recognized as a biological predictor of metastasis and poor prognosis for many different cancer types; however, the molecular mechanisms of how dysadherin affects cancer progression are still poorly understood. In this study, we examined whether AKT signaling could link dysadherin expression with downstream events that promote the metastatic potential of human breast cancer cells. Immunohistochemical analysis of breast cancer tissues showed that dysadherin expression was highly associated with elevated expression of phospho‐ AKT . The introduction of dysadherin c DNA into BT‐474, MCF‐7 and T‐47D breast cancer cell lines enhanced their levels of AKT phosphorylation, while knockdown of dysadherin in MDA‐MB‐231 and Hs578T breast cancer cell lines suppressed AKT phosphorylation. Treatment with the AKT inhibitor triciribine suppressed dysadherin‐mediated pro‐metastatic effects, including epithelial–mesenchymal transition, cell motility and drug resistance. These findings suggest that dysadherin might contribute to breast cancer progression through AKT activation. ( Cancer Sci 2012; 103: 1280–1289)