OBJECTIVE: The autophagy-associated release of HMGB1 (high-mobility group box 1) has been reported that protect cancer cells from numerous chemotherapeutics. However, the related molecular mechanism involved in the protection of oral cancer cells remains unclear. RESEARCH DESIGN AND METHODS: In this study, we determined that HMGB1 released by oral cancer cells protected the cells against apoptosis caused by vincristine by upregulating the transcription of Mcl-1. RESULTS: Extracellular HMGB1 seems to be required for the autophagy-mediated inhibition of apoptosis because the effect of autophagy protection was abolished by HMGB1 knockdown. Vincristine treatment increased the expression of Mcl-1 mRNA, but decreased the Mcl-1 protein expression. HMGB1 expression inhibited blocked the Mcl-1 transcription increase and reduced Mcl-1 expression, demonstrate that HMGB1 is required for the upregulation of Mcl-1 transcriptional, and thereby maintaining Mcl-1 protein expression levels is required for the survival of oral cancer cells by vincristine. CONCLUSIONS: Collectively, this study suggested that the HMGB1-mediated Mcl-1 transcription upregulation is a key mechanism by which autophagy protects oral cancer cells against vincristine-induced apoptosis.
OBJECTIVE: The autophagy-associated release of HMGB1 (high-mobility group box 1) has been reported that protect cancer cells from numerous chemotherapeutics. However, the related molecular mechanism involved in the protection of oral cancer cells remains unclear. RESEARCH DESIGN AND METHODS: In this study, we determined that HMGB1 released by oral cancer cells protected the cells against apoptosis caused by vincristine by upregulating the transcription of Mcl-1. RESULTS: Extracellular HMGB1 seems to be required for the autophagy-mediated inhibition of apoptosis because the effect of autophagy protection was abolished by HMGB1 knockdown. Vincristine treatment increased the expression of Mcl-1 mRNA, but decreased the Mcl-1 protein expression. HMGB1 expression inhibited blocked the Mcl-1 transcription increase and reduced Mcl-1 expression, demonstrate that HMGB1 is required for the upregulation of Mcl-1 transcriptional, and thereby maintaining Mcl-1 protein expression levels is required for the survival of oral cancer cells by vincristine. CONCLUSIONS: Collectively, this study suggested that the HMGB1-mediated Mcl-1 transcription upregulation is a key mechanism by which autophagy protects oral cancer cells against vincristine-induced apoptosis.
Entities:
Keywords:
Mcl-1; apoptosis; autophagy; high-mobility group box 1; vincristine