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Altered death receptor signaling promotes epithelial-to-mesenchymal transition and acquired chemoresistance.

Abstract：

:Altered death receptor signaling and resistance to subsequent apoptosis is an important clinical resistance mechanism. Here, we investigated the role of death receptor resistance in breast cancer progression. Resistance of the estrogen receptor alpha (ER)-positive, chemosensitive MCF7 breast cancer cell line to tumor necrosis factor (TNF) was associated with loss of ER expression and a multi-drug resistant phenotype. Changes in three major pathways were involved in this transition to a multidrug resistance phenotype: ER, Death Receptor and epithelial to mesenchymal transition (EMT). Resistant cells exhibited altered ER signaling, resulting in decreased ER target gene expression. The death receptor pathway was significantly altered, blocking extrinsic apoptosis and increasing NF-kappaB survival signaling. TNF resistance promoted EMT changes, resulting in a more aggressive phenotype. This first report identifying specific mechanisms underlying acquired resistance to TNF could lead to a better understanding of the progression of breast cancer in response to chemotherapy treatment.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Antoon JW,Lai R,Struckhoff AP,Nitschke AM,Elliott S,Martin EC,Rhodes LV,Yoon NS,Salvo VA,Shan B,Beckman BS,Nephew KP,Burow ME

doi

10.1038/srep00539

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

539

issn

2045-2322

journal_volume

2

pub_type

杂志文章

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