TCTP is a critical survival factor that protects cancer cells from oxidative stress-induced cell-death

The translationally controlled tumor protein (TCTP) displays growth-promoting and antiapoptotic properties. To gain information on the role of TCTP in cancer disease, we studied the modulation of TCTP and cell survival under stress conditions on tumor cell lines of different origins. When cancer cells were exposed to a mild oxidative stress, such low doses of Arsenic trioxide (ATO) or hydrogen peroxide (H2O2), up-regulation of TCTP was observed in cells survived to the treatment. Differently, a strong oxidative hit provided by ATO combined with glutathione (GSH) depletion or condition of glucose deprivation caused a down-modulation of TCTP followed by cell death.Clones with a forced expression of TCTP or with silenced TCTP were obtained from the breast cancer cell line MDA-MB-231. The sensitivity to oxidative stress was strongly enhanced in down-modulated TCTP cells while decreasing in cells with high levels of TCTP.Together these results indicate that TCTP is a survival factor that protects cancer cells from oxidative stress-induced cell-death. We propose TCTP as a “stress hallmark” that may be exploited as a therapeutic target to decrease the resistance of cancer cells to anticancer therapy.

► We characterize for the first time the translationally controlled tumor protein (TCTP) as a stress hallmark of tumor cells.
► High TCTP levels confer a survival advantage in cancer cells under stress conditions.
► TCTP induction by As2O3 contributes to the resistant phenotype of tumor cells.
► TCTP-deficient cells are highly susceptible to oxidative and metabolic stress.
► TCTP inhibitors may improve outcome in cancer treatment with conventional chemotherapeutics.