title: Sustained overexpression of Redd1 leads to Akt activation involved in cell survival.
abstract: Herein, we show that the constitutive overexpression of Redd1, a negative regulator of mTORC1, induces Akt activation in lung cancer cells. Akt phosphorylation was reduced to basal levels by Rictor siRNA, suggesting the involvement of mTORC2 in this process. Perifosine and PP242, selective inhibitors of Akt and mTORC1/2, respectively, efficiently suppressed the Akt phosphorylation that was induced by the sustained overexpression of Redd1 and increased the sensitivity of the cells to cisplatin. Therefore, the sustained overexpression of Redd1 leads to mTORC1 inhibition and to consequent Akt activation that is involved in cell survival. This finding highlights the importance of Akt activation as a therapeutic target to overcome resistance to chemotherapy.
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul 139-706, Republic of Korea. hyeonok@kirams.re.kr
authors.forename: Hyeon-Ok
authors.initials: HO
authors.lastname: Jin
authors.forename: Sung-Eun
authors.initials: SE
authors.lastname: Hong
authors.forename: Jae-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Ha-Na
authors.initials: HN
authors.lastname: Choi
authors.forename: Karam
authors.initials: K
authors.lastname: Kim
authors.forename: Sungkwan
authors.initials: S
authors.lastname: An
authors.forename: Tae-Boo
authors.initials: TB
authors.lastname: Choe
authors.forename: Chang-Sun
authors.initials: CS
authors.lastname: Hwang
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Jong-Il
authors.initials: JI
authors.lastname: Kim
authors.forename: Hyun-Ah
authors.initials: HA
authors.lastname: Kim
authors.forename: Eun-Kyu
authors.initials: EK
authors.lastname: Kim
authors.forename: Woo Chul
authors.initials: WC
authors.lastname: Noh
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Hong
authors.forename: Seok-Il
authors.initials: SI
authors.lastname: Hong
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Lee
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Park
mesh_terms: D002470:Cell Survival / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism*; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D046912:Multiprotein Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: C469991:DDIT4 protein, human; D046912:Multiprotein Complexes; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D002945:Cisplatin