A Positive Feedback Loop between Sestrin2 and mTORC2 Is Required for theSurvival of Glutamine-Depleted Lung Cancer Cells

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/473903.do
DOI
10.1016/j.celrep.2017.06.066
Title
A Positive Feedback Loop between Sestrin2 and mTORC2 Is Required for theSurvival of Glutamine-Depleted Lung Cancer Cells
Description
This work was supported by grants NRF-2015R1A2A1A15053422 andNRF-2015R1A2A1A10052745 from the National Research Foundation of Korea,funded by the Ministry of Science, ICT, and Future Planning; by grantNRF-2017R1A6A3A04010231 from the National Research Foundation of Korea,funded by Ministry of Education; and by grants HI16C1501 and HI15C0001from the Korea Health Technology R&D Project through the Korea HealthIndustry Development Institute (KHIDI), funded by the Ministry of Healthand Welfare, Republic of Korea. The biospecimens for this study wereprovided by the Keimyung University Dongsan Hospital Korea RegionalBiobank, a member of the National Biobank of Korea, which is supportedby the Ministry of Health and Welfare. All samples derived from NationalBiobank of Korea were obtained with informed consent under IRB-approvedprotocols.
abstract
Proper regulation of mTORC1 and mTORC2 upon nutrient starvation is critical for cancer cell survival. Upregulation of Sestrin2 in response to glutamine deprivation rescues cell death by suppressing mTORC1. However, the contribution of mTORC2 to Sestrin2-mediated mTORC1 suppression remains unclear. Here, we report that both Sestrin2 and mTORC2 are upregulated in glutamine-depleted lung cancer cells. Moreover, glutamine depletion caused Sestrin2 to associate with mTORC2, which was required for the increase in Sestrin2 protein stability and the reduction in mTORC1 activity. Ultimately, differential regulation of mTORC1 and 2 by Sestrin2 reprogramed lipid metabolism and enabled glutamine-depleted lung cancer cells to survive by maintaining energy and redox balance. Importantly, combined inhibition of glutamine utilization and Sestrin2 induced lung cancer cell death both in vitro and in vivo. This study shows that differential Sestrin2-mediated regulation of mTORC1 and mTORC2 is necessary for the survival of glutamine-depleted lung cancer cells.
provenance
Made available in Cube on 2018-09-28T10:31:57Z (GMT). No. of bitstreams: 0
language
English
author
Byun, Jun-Kyu
Choi, Yeon-Kyung
Kim, Ji-Hyun
Jeong, Ji Yun
Jeon, Hui-Jeon
Kim, Mi-Kyung
Hwang, Ilseon
Lee, Shin-Yup
Lee, You Mie
Lee, In-Kyu
Park, Keun-Gyu
accessioned
2018-09-28T10:31:57Z
available
2018-09-28T10:31:57Z
issued
2017
citation
CELL REPORTS(20): 3
issn
2211-1247
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/473903.do
Funder
보건복지부
Funding Program
선도형특성화연구사업
Project ID
1465023227
Jurisdiction
Rep.of Korea
Project Name
Efficacy assessment and drug development for metabolic liver disease
rights
openAccess
type
article


Files in This Item

There are no attached files.