Title: Abstract 3793: Overexpression of A20 and activated-Src result in TRAIL resistance in oral cancer cells
Abstract: Abstract The 5-year survival rate for oral cancer patients is around 50%, and has remained unchanged for the last several decades. This poor survival rate is due to the delay in diagnosis, the high incidence of recurrence, and the difficulty of controlling metastases. It is considered that the acquisition of resistance to anoikis and apoptosis is an essential event to successfully metastasize. We have to withdraw these resistance of cancer cells to improve the survival ratio. In this study, we have used oral squamous cell carcinoma cell lines with and without distinct metastatic ability, and revealed the relationship between their anoikis and apoptosis sensitivity and the metastatic ability. At first we examined their sensitivity to anoikis by using the low attachment culture condition. There was no apparent relation between their metastatic potential and the sensitivity to anoikis. SAS cells which have no metastatic potency showed modest sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), whereas SAS-T5 cells and SAS-L1 cells, a clone with high metastatic potential showed robust resistance. Fas ligand (Anti-Fas/CD95 monoclonal antibody) showed the similar effects for apoptosis induction as well as TRAIL, but TNF-α had no effect in these cells. We confirmed that the expression levels and the localization of TRAIL receptors were not correlated with TRAIL sensitivity. We found that the mechanisms underlying the differences in these resistance to TRAIL was an activity of Src kinase and the basal levels of A20. Phosphorylated Src (Tyr 416), the active form, was upregulated in SAS-T5 and SAS-L1 cells compared to parental SAS cells. Src inhibitor PP2 suppressed cell proliferation in response to dependence on Src signaling. Downregulation of Src or A20 with siRNA made metastatic cells dissolve the resistance to TRAIL-induced apoptosis. These results suggest that combination therapy with TRAIL and some drug inhibiting Src kinase and /or A20 expression may be a treatment strategy for oral squamous cell carcinoma. Citation Format: Satoshi Hino, Tomohiro Hamakawa, Koh-ichi Nakashiro, Hiroyuki Hamakawa. Overexpression of A20 and activated-Src result in TRAIL resistance in oral cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3793. doi:10.1158/1538-7445.AM2015-3793
Publication Year: 2015
Publication Date: 2015-08-01
Language: en
Type: article
Indexed In: ['crossref']
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