Journal
ONCOGENE
Volume 32, Issue 26, Pages 3130-3138Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2012.327
Keywords
MEMO1; IRS1; EMT; Snail1; breast cancer
Funding
- Era of Hope Research award [W81XWH-09-1-0409]
- Department of Defense [W81XWH-05-1-0470]
- MD Anderson's Cancer Center Support Grant [CA016672]
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MEMO1 (mediator of ErbB2-driven cell motility 1) regulates HER2-dependent cell migration. Increased MEMO1 expression is associated with cancer aggressiveness. Here, we found that MEMO1 is also involved in breast carcinogenesis via regulating insulin-like growth factor-I receptor-dependent signaling events. We showed that MEMO1 binds to insulin receptor substrate 1, activates the downstream PI3K/Akt signaling pathway, leads to upregulation of Snail1 and thereby triggers the epithelial-mesenchymal transition (EMT) program. In addition, MEMO1 overexpression is accompanied by growth factor-independent proliferation, anchorage-independent growth in soft agar, and enhanced metastatic potential. Together, these findings suggest that MEMO1 acts as an oncogene and is a potential therapeutic target for cancer treatment.
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