Cross-talk between PI3K/Akt and MEK/ERK pathways mediates endoplasmic reticulum stress-induced cell cycle progression and cell death in human hepatocellular carcinoma cells

  • Authors:
    • Rongyang Dai
    • Run Chen
    • Hong Li
  • View Affiliations

  • Published online on: June 1, 2009     https://doi.org/10.3892/ijo_00000306
  • Pages: 1749-1757
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Abstract

The unfolded protein response (UPR) is a conserved adaptive response utilized by cells to cope with endoplasmic reticulum (ER) stress. In addition to the UPR, cells also trigger other adaptive responses under ER stress conditions. Although the PI3K/Akt and MEK/ERK pathways are known to protect cells from ER stress-induced apoptosis, their other functions under ER stress remain elusive. Here, we showed that long-term ER stress resulted in inactivation of Akt and activation of ERK in human hepatocellular carcinoma (HCC) cells. Importantly, both PI3K inhibitor LY294002 and dominant-negative Akt construct promoted tunicamycin- and thapsigargin-induced ERK phosphorylation. In addition, constitutively active Akt construct inhibited ER stress-induced ERK phosphorylation. We also showed that ER stress-induced PI3K/Akt inactivation contributed to cell cycle arrest and MEK/ERK inhibition moderately increased cell percentage in the S phase. It is notable that U0126 made HCC cells much more sensitive to ER stress-induced apoptosis than LY294002. Taken together, our results indicate that there is cross-talk between the PI3K/Akt and MEK/ERK cascades under ER stress in HCC cells, which contributes to both cell cycle arrest and cell survival. We propose that ER stress-induced cross-talk between the PI3K/Akt and MEK/ERK cascades is a protective mechanism utilized by HCC cells to adapt to stress.

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June 2009
Volume 34 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Dai R, Chen R and Li H: Cross-talk between PI3K/Akt and MEK/ERK pathways mediates endoplasmic reticulum stress-induced cell cycle progression and cell death in human hepatocellular carcinoma cells. Int J Oncol 34: 1749-1757, 2009
APA
Dai, R., Chen, R., & Li, H. (2009). Cross-talk between PI3K/Akt and MEK/ERK pathways mediates endoplasmic reticulum stress-induced cell cycle progression and cell death in human hepatocellular carcinoma cells. International Journal of Oncology, 34, 1749-1757. https://doi.org/10.3892/ijo_00000306
MLA
Dai, R., Chen, R., Li, H."Cross-talk between PI3K/Akt and MEK/ERK pathways mediates endoplasmic reticulum stress-induced cell cycle progression and cell death in human hepatocellular carcinoma cells". International Journal of Oncology 34.6 (2009): 1749-1757.
Chicago
Dai, R., Chen, R., Li, H."Cross-talk between PI3K/Akt and MEK/ERK pathways mediates endoplasmic reticulum stress-induced cell cycle progression and cell death in human hepatocellular carcinoma cells". International Journal of Oncology 34, no. 6 (2009): 1749-1757. https://doi.org/10.3892/ijo_00000306