Differential expression patterns of the short and long isoform of cFLIP on FasL‑mediated apoptosis.

Oncol Rep 2018 May 16;39(5):2443-2449. Epub 2018 Mar 16.

Department of Immunology, School of Medicine, Keimyung University, Dalseo‑gu, Daegu 704‑701, Republic of Korea.

cFLIP is a key regulator of the anti‑apoptotic mechanism and its association with FAS‑mediated apoptosis has been widely studied and well documented. However, the equipoise between its two isoforms i.e. the long isoform cFLIP(L) and the short isoform cFLIP(S) during FAS‑mediated apoptosis remains to be revealed. Therefore, the present study aimed to investigate the regulatory effect of these isoforms on FasL‑mediated apoptosis in renal carcinoma. Our results revealed that FasL treatment to Caki cells induced the expression of cFLIP(S) and downregulated the expression of cFLIP(L) in a concentration‑ and time‑dependent manner. Furthermore, our results indicated that cell death receptor‑mediated apoptosis inducers such as TNF‑α and TRAIL, induced apoptosis in Caki cells along with downregulation of cFLIP(L), however, they had no effect on the expression of cFLIP(S). In addition, FasL‑mediated cFLIP(L) downregulation was prevented by pan‑caspase inhibitor (z‑VAD‑fmk), however pan‑caspase inhibitor did not have an effect on FasL‑induced cFLIP(S) upregulation. Furthermore, FasL induced upregulation of the expression of cFLIP(S) at the post‑translational level. Furthermore, pretreatment of Caki cells with ROS scavengers (N‑acetylcysteine and glutathione) prevented the downregulation of cFLIP(L), the upregulation of cFLIP(S) and apoptosis induced by FasL. Collectively, these data indicated that a novel pathway of cFLIP(L)/(S) differential expression pattern was associated with FasL‑induced apoptosis and modulated by ROS generation.

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http://dx.doi.org/10.3892/or.2018.6317DOI Listing
May 2018
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