TY - JOUR
T1 - TRAP1 regulates proliferation, mitochondrial function, and has prognostic significance in NSCLC
AU - Agorreta, Jackeline
AU - Hu, Jianting
AU - Liu, Dongxia
AU - Delia, Domenico
AU - Turley, Helen
AU - Ferguson, David J P
AU - Iborra, Francisco
AU - Pajares, María J.
AU - Larrayoz, Marta
AU - Zudaire, Isabel
AU - Pio, Ruben
AU - Montuenga, Luis M.
AU - Harris, Adrian L.
AU - Gatter, Kevin
AU - Pezzella, Francesco
PY - 2014
Y1 - 2014
N2 - The TNF receptor-associated protein 1 (TRAP1) is a mitochondrial HSP that has been related to drug resistance and protection from apoptosis in colorectal and prostate cancer. Here, the effect of TRAP1 ablation on cell proliferation, survival, apoptosis, and mitochondrial function was determined in non-small cell lung cancer (NSCLC). In addition, the prognostic value of TRAP1 was evaluated in patients with NSCLC. These results demonstrate that TRAP1 knockdown reduces cell growth and clonogenic cell survival. Moreover, TRAP1 downregulation impairs mitochondrial functions such as ATP production and mitochondrial membrane potential as measured byTMRM(tetramethylrhodamine methylester) uptake, but it does not affect mitochondrial density or mitochondrial morphology. The effect of TRAP1 silencing on apoptosis, analyzed by flow cytometry and immunoblot expression (cleaved PARP, caspase-9, and caspase-3) was cell line and context dependent. Finally, the prognostic potential of TRAP1 expression in NSCLC was ascertained via immunohistochemical analysis which revealed that high TRAP1 expression was associated with increased risk of disease recurrence (univariate analysis, P = 0.008; multivariate analysis, HR: 2.554; 95% confidence interval, 1.085-6.012; P = 0.03). In conclusion, these results demonstrate that TRAP1 impacts the viability of NSCLC cells, and that its expression is prognostic in NSCLC.
AB - The TNF receptor-associated protein 1 (TRAP1) is a mitochondrial HSP that has been related to drug resistance and protection from apoptosis in colorectal and prostate cancer. Here, the effect of TRAP1 ablation on cell proliferation, survival, apoptosis, and mitochondrial function was determined in non-small cell lung cancer (NSCLC). In addition, the prognostic value of TRAP1 was evaluated in patients with NSCLC. These results demonstrate that TRAP1 knockdown reduces cell growth and clonogenic cell survival. Moreover, TRAP1 downregulation impairs mitochondrial functions such as ATP production and mitochondrial membrane potential as measured byTMRM(tetramethylrhodamine methylester) uptake, but it does not affect mitochondrial density or mitochondrial morphology. The effect of TRAP1 silencing on apoptosis, analyzed by flow cytometry and immunoblot expression (cleaved PARP, caspase-9, and caspase-3) was cell line and context dependent. Finally, the prognostic potential of TRAP1 expression in NSCLC was ascertained via immunohistochemical analysis which revealed that high TRAP1 expression was associated with increased risk of disease recurrence (univariate analysis, P = 0.008; multivariate analysis, HR: 2.554; 95% confidence interval, 1.085-6.012; P = 0.03). In conclusion, these results demonstrate that TRAP1 impacts the viability of NSCLC cells, and that its expression is prognostic in NSCLC.
UR - http://www.scopus.com/inward/record.url?scp=84900454075&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84900454075&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-13-0481
DO - 10.1158/1541-7786.MCR-13-0481
M3 - Article
C2 - 24567527
AN - SCOPUS:84900454075
VL - 12
SP - 660
EP - 669
JO - Molecular Cancer Research
JF - Molecular Cancer Research
SN - 1541-7786
IS - 5
ER -