TRAP1 regulates autophagy in lung cancer cells

Abstract Background Expression of TRAP 1, a member of the HSP 90 chaperone family, has been implicated in tumour protective effects, based on its differential mitochondrial localization and function. Design This work was designed to provide new insights into the pathways involved in TRAP 1‐provided cytoprotection on NSCLC . For this, TRAP 1‐depleted A549 human NSCLC cells and MRC ‐5 normal lung fibroblasts were produced using a si RNA approach and main cellular quality control mechanisms were investigated. Results TRAP 1‐depleted A549 cells displayed decreased cell viability likely due to impaired mitochondrial function including decreased ATP / AMP ratio, oxygen consumption and membrane potential, as well as increased apoptotic indicators. Furthermore, the negative impact of TRAP 1 depletion on mitochondrial function was not observed in normal MRC ‐5 lung cells, which might be due to the differential intracellular localization of the chaperone in tumour versus normal cells. Additionally, A549 TRAP 1‐depleted cells showed increased autophagic flux. Functionally, autophagy inhibition resulted in decreased cell viability in both TRAP 1‐expressing and TRAP 1‐depleted tumour cells with minor effects on MRC ‐5 cells. Conversely, autophagy stimulation decreased cell viability of both A549 and MRC ‐5 TRAP 1‐expressing cells while in A549 TRAP 1‐depleted cells, increased autophagy augmented viability. Conclusions Our results show that even though TRAP 1 depletion affects both normal MRC ‐5 and tumour A549 cell proliferation, inhibition of autophagy per se led to a decrease in tumour cell mass, while having a reduced effect on the normal cell line. The strategy of targeting TRAP 1 in NSCLC shows future potential therapeutic applications.