FHIT loss confers cisplatin resistance in lung cancer via the AKT/NF-κB/Slug-mediated PUMA reduction

doi:10.1038/onc.2014.184

中山醫學大學機構典藏 CSMUIR > 醫學院 > 醫學系 > 期刊論文 > Item 310902500/18188

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/18188

Title:	FHIT loss confers cisplatin resistance in lung cancer via the AKT/NF-κB/Slug-mediated PUMA reduction
Authors:	Wu, D.-W.;Lee, M.-C.;Hsu, N.-Y.;Wu, T.-C.;Wu, J.-Y.;Wang, Y.-C.;Cheng, Y.-W.;Chen, Chen C.-Y.;Lee, H.
Date:	2015
Issue Date:	2017-08-08T09:49:21Z (UTC)
Publisher:	Nature Publishing Group
ISSN:	9509232
Abstract:	Fragile histidine triad (FHIT) loss by the two-hit mechanism of loss of heterozygosity and promoter hypermethylation commonly occurrs in non-small cell lung cancer (NSCLC) and may confer cisplatin resistance in NSCLC cells. However, the underlying mechanisms of FHIT loss in cisplatin resistance and the response to cisplatin-based chemotherapy in NSCLC patients have not yet been reported. In the present study, inhibition concentration of 50% cell viability induced by cisplatin (IC50) and soft agar growth and invasion capability were increased and decreased in FHIT-knockdown and -overexpressing cells, respectively. Mechanistically, Slug transcription is upregulated by AKT/NF-κB activation due to FHIT loss and, in turn, Slug suppresses PUMA expression; this decrease of PUMA by FHIT loss is responsible for cisplatin resistance. In addition, cisplatin resistance due to FHIT loss can be conquered by AKT inhibitor - perifosine in xenograft tumors. Among NSCLC patients, low FHIT, high p-AKT, high Slug and low PUMA were correlated with shorter overall survival, relapse-free survival and poorer response to cisplatin-based chemotherapy. Therefore, the AKT inhibitor perifosine might potentially overcome the resistance to cisplatin-based chemotherapy in NSCLC patients with low-FHIT tumors, and consequently improve the outcome. © 2015 Macmillan Publishers Limited All rights reserved.
URI:	http://dx.doi.org/10.1038/onc.2014.184 https://www.scopus.com/inward/record.uri?eid=2-s2.0-84938089515&doi=10.1038%2fonc.2014.184&partnerID=40&md5=4d62a0199153b0097e08e42c67b10b43 https://ir.csmu.edu.tw:8080/ir/handle/310902500/18188
Relation:	Oncogene 34(19) ,2505-2515
Appears in Collections:	[醫學系] 期刊論文

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