TRAP1 Regulates Autophagy in Lung Cancer Cells.

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TRAP1 Regulates Autophagy in Lung Cancer Cells.

Eur J Clin Invest. 2018 Jan 31;:

Authors: Barbosa IA, Vega-Naredo I, Loureiro R, Branco AF, Garcia R, Scott PM, Oliveira PJ

Abstract
BACKGROUND: Expression of TRAP1, a member of the HSP90 chaperone family, has been implicated in tumor protective effects, based on differential mitochondrial localization and function.
DESIGN: This work was designed to provide new insights on the pathways involved in TRAP1-provided cytoprotection on NSCLC. For this, TRAP1-depleted A549 human NSCLC cells and MRC-5 normal lung fibroblasts were produced using a siRNA approach and main cellular quality control mechanisms were investigated.
RESULTS: TRAP1-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 TRAP1 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 tumor versus normal cells. Additionally, A549 TRAP1-depleted cells showed increased autophagic flux. Functionally, autophagy inhibition resulted in decreased cell viability in both TRAP1-expressing and TRAP1-depleted tumor cells with minor effects on MRC-5 cells. Conversely, autophagy stimulation decreased cell viability of both A549 and MRC-5 TRAP1-expressing cells while in A549 TRAP1-depleted cells, increased autophagy augmented viability.
CONCLUSIONS: Our results show that even though TRAP1 depletion affects both normal MRC-5 and tumor A549 cell proliferation, inhibition of autophagy per se led to a decrease in tumor cell mass, while having a reduced effect on the normal cell line. The strategy of targeting TRAP1 in NSCLC shows future potential therapeutic applications. This article is protected by copyright. All rights reserved.

PMID: 29383696 [PubMed - as supplied by publisher]

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