1. C-FLIP(L) contributes to TRAIL resistance in HER2-positive breast cancer
- Author
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Xue Leng, Xiyin Wei, Man Yu, Baocun Sun, and Fenglin Zang
- Subjects
Receptor, ErbB-2 ,Biophysics ,CASP8 and FADD-Like Apoptosis Regulating Protein ,Apoptosis ,Breast Neoplasms ,Biology ,Biochemistry ,TNF-Related Apoptosis-Inducing Ligand ,Breast cancer ,Downregulation and upregulation ,medicine ,Tumor Cells, Cultured ,Humans ,skin and connective tissue diseases ,Receptor ,Molecular Biology ,Cell Biology ,medicine.disease ,Phenotype ,SKBR3 ,Flip ,Drug Resistance, Neoplasm ,Immunology ,Cancer research ,Trail resistance ,Female - Abstract
Breast cancers with HER2 amplification have a poorer prognosis than the luminal phenotypes. TRAIL activates apoptosis upon binding its receptors in some but not all breast cancer cell lines. Herein, we investigated the expression pattern of c-FLIP(L) in a cohort of 251 invasive breast cancer tissues and explored its potential role in TRAIL resistance. C-FLIP(L) was relatively high-expressed in HER2-positive breast cancer in comparison with other molecular subtypes, co-expressed with TRAIL death receptors, and inversely correlated with the apoptosis index. Downregulation of c-FLIP(L) sensitized SKBR3 cells to TRAIL-induced apoptosis in a concentration- and time-dependent manner and enhanced the activities and cleavages of caspase-8 and caspase-3, without altering the surface expression of death receptors. Together, our results indicate that c-FLIP(L) promotes TRAIL resistance and inhibits caspase-3 and caspase-8 activation in HER2-positive breast cancer.
- Published
- 2014