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Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Jang, Se-Kyeong | - |
dc.contributor.author | Hong, Sung-Eun | - |
dc.contributor.author | Lee, Da-Hee | - |
dc.contributor.author | Kim, Ji-Young | - |
dc.contributor.author | Kim, Ji Yea | - |
dc.contributor.author | Ye, Sang-Kyu | - |
dc.contributor.author | Hong, Jungil | - |
dc.contributor.author | Park, In-Chul | - |
dc.contributor.author | Jin, Hyeon-Ok | - |
dc.date.accessioned | 2021-08-23T01:16:16Z | - |
dc.date.available | 2021-08-23T10:19:37Z | - |
dc.date.issued | 2021-07-12 | - |
dc.identifier.citation | BMC Cancer. 2021 Jul 12;21(1):803 | ko_KR |
dc.identifier.issn | 1471-2407 | - |
dc.identifier.uri | https://hdl.handle.net/10371/174818 | - |
dc.description.abstract | Background
Although the major anticancer effect of metformin involves AMPK-dependent or AMPK-independent mTORC1 inhibition, the mechanisms of action are still not fully understood. Methods To investigate the molecular mechanisms underlying the effect of metformin on the mTORC1 inhibition, MTT assay, RT-PCR, and western blot analysis were performed. Results Metformin induced the expression of ATF4, REDD1, and Sestrin2 concomitant with its inhibition of mTORC1 activity. Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment. Moreover, REDD1- and Sestrin2-mediated mTORC1 inhibition in response to metformin was independent of AMPK activation. Additionally, lapatinib enhances cell sensitivity to metformin, and knockdown of REDD1 and Sestrin2 decreased cell sensitivity to metformin and lapatinib. Conclusions ATF4-induced REDD1 and Sestrin2 expression in response to metformin plays an important role in mTORC1 inhibition independent of AMPK activation, and this signalling pathway could have therapeutic value. | ko_KR |
dc.description.sponsorship | This research was supported by grants from the Korea Institute of Radiological and Medical Sciences (KIRAMS), funded by the Ministry of Science and ICT (MSIT), Republic of Korea (Nos. 50336–2021; 50531–2021; and 50544–2021). | ko_KR |
dc.language.iso | en | ko_KR |
dc.publisher | BMC | ko_KR |
dc.subject | AMPK | - |
dc.subject | Metformin | - |
dc.subject | mTORC1 | - |
dc.subject | REDD1 | - |
dc.subject | Sestrin2 | - |
dc.title | Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin | ko_KR |
dc.type | Article | ko_KR |
dc.contributor.AlternativeAuthor | 장세경 | - |
dc.contributor.AlternativeAuthor | 홍성은 | - |
dc.contributor.AlternativeAuthor | 이다희 | - |
dc.contributor.AlternativeAuthor | 김지영 | - |
dc.contributor.AlternativeAuthor | 김지예 | - |
dc.contributor.AlternativeAuthor | 예상규 | - |
dc.contributor.AlternativeAuthor | 홍정일 | - |
dc.contributor.AlternativeAuthor | 박인철 | - |
dc.contributor.AlternativeAuthor | 진현옥 | - |
dc.identifier.doi | 10.1186/s12885-021-08346-x | - |
dc.citation.journaltitle | BMC Cancer | ko_KR |
dc.language.rfc3066 | en | - |
dc.rights.holder | The Author(s) | - |
dc.date.updated | 2021-07-20T07:03:52Z | - |
dc.citation.number | 1 | ko_KR |
dc.citation.startpage | 803 | ko_KR |
dc.citation.volume | 21 | ko_KR |
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