YBX1 mediates autophagy by targeting p110β and decreasing the sensitivity to cisplatin in NSCLC
Open Access
- 19 June 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Disease
- Vol. 11 (6), 1-14
- https://doi.org/10.1038/s41419-020-2555-4
Abstract
Y-box binding protein 1 (YBX1) is involved in the development of multiple types of tumors. However, the relationship between YBX1 and autophagy in non-small cell lung cancer (NSCLC) remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and markers of autophagy (LC3I/II) in NSCLC and examined their roles in regulating sensitivity to cisplatin in NSCLC. The retrospective analysis of patients with NSCLC indicated that YBX1 was positively correlated with autophagy. Increased levels of YBX1 or autophagy also observed in NSCLC cells compared with those in 16HBE cells. Compared to the controls, the knockdown of YBX1 expression suppressed autophagy, increased drug sensitivity and promoted apoptosis in response to cisplatin in NSCLC cells by targeting the p110β promoter and inhibiting p110β/Vps34/beclin1 signaling pathways. We also demonstrated in an in vivo study that the overexpressed YBX1 effectively increased NSCLC growth and progression and decreased the sensitivity to cisplatin by inducing autophagy in a xenograft tumor model, and these effects were concomitant with the increasing of p110β and beclin1 expression. Collectively, these results show that YBX1 plays an essential role in autophagy in NSCLC.Keywords
This publication has 41 references indexed in Scilit:
- YB-1 Synthesis Is Regulated by mTOR Signaling PathwayPLOS ONE, 2012
- Autophagy modulation as a potential therapeutic target for diverse diseasesNature Reviews Drug Discovery, 2012
- Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver functionProceedings of the National Academy of Sciences of the United States of America, 2012
- Measurements of Tumor Cell Autophagy Predict Invasiveness, Resistance to Chemotherapy, and Survival in MelanomaClinical Cancer Research, 2011
- Principles and Current Strategies for Targeting Autophagy for Cancer TreatmentClinical Cancer Research, 2011
- Human AP endonuclease (APE1/Ref-1) and its acetylation regulate YB-1-p300 recruitment and RNA polymerase II loading in the drug-induced activation of multidrug resistance gene MDR1Oncogene, 2010
- Autophagy in Vascular DiseaseProceedings of the American Thoracic Society, 2010
- The role of autophagy in tumour development and cancer therapyExpert Reviews in Molecular Medicine, 2009
- Regulatory Role of Human AP-Endonuclease (APE1/Ref-1) in YB-1-Mediated Activation of the Multidrug Resistance Gene MDR1Molecular and Cellular Biology, 2008
- Role and Regulation of Starvation-Induced Autophagy in the Drosophila Fat BodyDevelopmental Cell, 2004