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

James W. Antoon, Rongye Lai, Amanda P. Struckhoff, Ashley M. Nitschke, Steven Elliott, Elizabeth C. Martin, Lyndsay V. Rhodes, Nam Seung Yoon, Virgilio A. Salvo, Bin Shan, Barbara S. Beckman, Kenneth Nephew, Matthew E. Burow

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Article number539
JournalScientific Reports
Volume2
DOIs
StatePublished - 2012

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Death Domain Receptors
Epithelial-Mesenchymal Transition
Estrogen Receptor alpha
Tumor Necrosis Factor-alpha
Breast Neoplasms
Phenotype
Apoptosis
NF-kappa B
Multiple Drug Resistance
Gene Expression
Drug Therapy
Cell Line
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

Antoon, J. W., Lai, R., Struckhoff, A. P., Nitschke, A. M., Elliott, S., Martin, E. C., ... Burow, M. E. (2012). Altered death receptor signaling promotes epithelial-to-mesenchymal transition and acquired chemoresistance. Scientific Reports, 2, [539]. https://doi.org/10.1038/srep00539

Altered death receptor signaling promotes epithelial-to-mesenchymal transition and acquired chemoresistance. / Antoon, James W.; Lai, Rongye; Struckhoff, Amanda P.; Nitschke, Ashley M.; Elliott, Steven; Martin, Elizabeth C.; Rhodes, Lyndsay V.; Yoon, Nam Seung; Salvo, Virgilio A.; Shan, Bin; Beckman, Barbara S.; Nephew, Kenneth; Burow, Matthew E.

In: Scientific Reports, Vol. 2, 539, 2012.

Research output: Contribution to journalArticle

Antoon, JW, Lai, R, Struckhoff, AP, Nitschke, AM, Elliott, S, Martin, EC, Rhodes, LV, Yoon, NS, Salvo, VA, Shan, B, Beckman, BS, Nephew, K & Burow, ME 2012, 'Altered death receptor signaling promotes epithelial-to-mesenchymal transition and acquired chemoresistance', Scientific Reports, vol. 2, 539. https://doi.org/10.1038/srep00539
Antoon, James W. ; Lai, Rongye ; Struckhoff, Amanda P. ; Nitschke, Ashley M. ; Elliott, Steven ; Martin, Elizabeth C. ; Rhodes, Lyndsay V. ; Yoon, Nam Seung ; Salvo, Virgilio A. ; Shan, Bin ; Beckman, Barbara S. ; Nephew, Kenneth ; Burow, Matthew E. / Altered death receptor signaling promotes epithelial-to-mesenchymal transition and acquired chemoresistance. In: Scientific Reports. 2012 ; Vol. 2.
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