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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Sustained overexpression of Redd1 leads to Akt activation involved in cell survival

Hyeon-Ok Jin1, Sung-Eun Hong, Jae-Hee Kim

  • 1Division 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

Cancer Letters
|March 27, 2013
PubMed

Insights

Sustained Redd1 overexpression in lung cancer cells inhibits mTORC1, activating Akt for cell survival. This Akt activation is crucial for overcoming chemotherapy resistance, highlighting it as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Redd1 negatively regulates mTORC1, a key cellular pathway.
  • Akt signaling is implicated in cancer cell survival and drug resistance.

Purpose of the Study:

  • To investigate the role of Redd1 overexpression in Akt activation in lung cancer.
  • To explore the therapeutic potential of targeting this pathway to overcome cisplatin resistance.

Main Methods:

  • Constitutive overexpression of Redd1 in lung cancer cells.
  • siRNA-mediated knockdown of Rictor to assess mTORC2 involvement.
  • Pharmacological inhibition of Akt (Perifosine) and mTORC1/2 (PP242).
  • Assessment of cell sensitivity to cisplatin.

Main Results:

  • Overexpression of Redd1 induced Akt phosphorylation in lung cancer cells.
  • Rictor siRNA reduced Akt phosphorylation, indicating mTORC2 involvement.
  • Inhibitors of Akt and mTORC1/2 suppressed Redd1-induced Akt phosphorylation and enhanced cisplatin sensitivity.

Conclusions:

  • Sustained Redd1 overexpression leads to mTORC1 inhibition and subsequent Akt activation, promoting cell survival.
  • Targeting Akt activation is a promising strategy to overcome chemotherapy resistance in lung cancer.

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