C-FLIP(L) contributes to TRAIL resistance in HER2-positive breast cancer |
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Authors: | Fenglin Zang Xiyin Wei Xue Leng Man Yu Baocun Sun |
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Affiliation: | 1. Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China;2. Princess Margaret Cancer Centre, University Health Network and University of Toronto, Toronto, Ontario M5G 2M9, Canada |
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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. |
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Keywords: | HER2-positive breast cancer TRAIL resistance C-FLIP(L) Apoptosis |
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