| Literature DB >> 27035620 |
M Hornsveld1, M Tenhagen2, R A van de Ven2, A M M Smits1, M H van Triest1, M van Amersfoort2, D E A Kloet1, T B Dansen1, B M Burgering1, P W B Derksen2.
Abstract
Loss of cellular adhesion leads to the progression of breast cancer through acquisition of anchorage independence, also known as resistance to anoikis. Although inactivation of E-cadherin is essential for acquisition of anoikis resistance, it has remained unclear how metastatic breast cancer cells counterbalance the induction of apoptosis without E-cadherin-dependent cellular adhesion. We report here that E-cadherin inactivation in breast cancer cells induces PI3K/AKT-dependent FOXO3 inhibition and identify FOXO3 as a novel and direct transcriptional activator of the pro-apoptotic protein BMF. As a result, E-cadherin-negative breast fail to upregulate BMF upon transfer to anchorage independence, leading to anoikis resistance. Conversely, expression of BMF in E-cadherin-negative metastatic breast cancer cells is sufficient to inhibit tumour growth and dissemination in mice. In conclusion, we have identified repression of BMF as a major cue that underpins anoikis resistance and tumour dissemination in E-cadherin-deficient metastatic breast cancer.Entities:
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Year: 2016 PMID： 27035620 PMCID： PMC5072425 DOI： 10.1038/cdd.2016.33
Source DB: PubMed Journal: Cell Death Differ ISSN： 1350-9047 Impact factor: 15.828