+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Cross-talk between PI3K/Akt and MEK/ERK pathways regulates human hepatocellular carcinoma cell cycle progression under endoplasmic reticulum stress



Cross-talk between PI3K/Akt and MEK/ERK pathways regulates human hepatocellular carcinoma cell cycle progression under endoplasmic reticulum stress



Zhonghua Gan Zang Bing Za Zhi 18(12): 909-914



To investigate the cross-talk between the PI3K/Akt and MEK/ERK pathways and its role in cell cycle regulation under endoplasmic reticulum stress in human hepatocellular carcinoma cells. PI3K inhibitor LY294002 and MEK inhibitor U0126 were used to block the PI3K/Akt and MEK/ERK pathways respectively, and constitutively activated Akt mutant construct was used to activate the PI3K/Akt pathway. Western blot was used to study the potential cross-talk between the PI3K/Akt and MEK/ERK pathways under endoplasmic reticulum stress in human hepatocellular carcinoma cells. the role of the cross-talk between the PI3K/Akt and MEK/ERK pathways in cell cycle regulation was investigated by using propidium iodide staining. LY294002 not only blocked Akt activation efficiently but also increased ERK phosphorylation markedly under endoplasmic reticulum stress in SMMC-7721 and Hep3B cells. Furthermore, myr-Akt inhibited endoplasmic reticulum stress-mediated ERK phosphorylation. In contrast, MEK inhibitor U0126 had no effect on endoplasmic reticulum stress-induced Akt activation. It is notable that both myr-Akt overexpression and MEK inhibitor U0126 inhibited endoplasmic reticulum stress-induced G0/G1 phase arrest in SMMC-7721 cells. Endoplasmic reticulum stress-induced Akt activation is mediated through PI3K and the PI3K/Akt pathway inactivation is involved in increased ERK activity in human hepatocellular carcinoma cells. The cross-talk between the PI3K/Akt and MEK/ERK cascades plays an important role in endoplasmic reticulum stress-induced human hepatocellular carcinoma cell cycle arrest.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 052391288

Download citation: RISBibTeXText

PMID: 21205476


Related references

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): 1749-1757, 2009

Oncolytic vaccinia virus inhibits human hepatocellular carcinoma MHCC97-H cell proliferation via endoplasmic reticulum stress, autophagy and Wnt pathways. Journal of Gene Medicine 18(9): 211-219, 2018

5-hydroxytryptamine 2B receptor regulates cell-cycle progression: cross-talk with tyrosine kinase pathways. Proceedings of the National Academy of Sciences of the United States of America 97(6): 2591-2596, 2000

Extract of Saccharina japonica induces apoptosis companied by cell cycle arrest and endoplasmic reticulum stress in SK-Hep1 human hepatocellular carcinoma cells. Asian Pacific Journal of Cancer Prevention 15(7): 2993-2999, 2015

Flavokawain C Inhibits Cell Cycle and Promotes Apoptosis, Associated with Endoplasmic Reticulum Stress and Regulation of MAPKs and Akt Signaling Pathways in HCT 116 Human Colon Carcinoma Cells. Plos One 11(2): E0148775, 2016

Exogenous H 2 S regulates endoplasmic reticulum-mitochondria cross-talk to inhibit apoptotic pathways in STZ-induced type I diabetes. American Journal of Physiology. Endocrinology and Metabolism 312(3): E190-E203, 2016

Cross-talk between two apoptotic pathways activated by endoplasmic reticulum stress: differential contribution of caspase-12 and AIF. Apoptosis 11(9): 1629-1641, 2006

Cross-talk between endoplasmic reticulum (ER) stress and the MEK/ERK pathway potentiates apoptosis in human triple negative breast carcinoma cells: role of a dihydropyrimidone, nifetepimine. Journal of Biological Chemistry 290(7): 3936-3949, 2015

TRB3 reverses chemotherapy resistance and mediates crosstalk between endoplasmic reticulum stress and AKT signaling pathways in MHCC97H human hepatocellular carcinoma cells. Oncology Letters 15(1): 1343-1349, 2018

Role of the Death Receptor and Endoplasmic Reticulum Stress Signaling Pathways in Polyphyllin I-Regulated Apoptosis of Human Hepatocellular Carcinoma HepG2 Cells. Biomed Research International 2018: 5241941-5241941, 2019

Temporal Cross Talk Between Endoplasmic Reticulum and Mitochondria Regulates Oxidative Stress and Mediates Microparticle-Induced Endothelial Dysfunction. Antioxidants and Redox Signaling 26(1): 15-27, 2016

Inhibitory cross-talk between the AMPK and ERK pathways mediates endoplasmic reticulum stress-induced insulin resistance in skeletal muscle. British Journal of Pharmacology 169(1): 69-81, 2014

Bicyclol induces cell cycle arrest and autophagy in HepG2 human hepatocellular carcinoma cells through the PI3K/AKT and Ras/Raf/MEK/ERK pathways. Bmc Cancer 16(1): 742, 2016

Selenium suppresses oxidative-stress-enhanced vascular smooth muscle cell calcification by inhibiting the activation of the PI3K/AKT and ERK signaling pathways and endoplasmic reticulum stress. Journal of Biological Inorganic Chemistry 19(3): 375-388, 2014

Enhanced autophagic flux by endoplasmic reticulum stress in human hepatocellular carcinoma cells contributes to the maintenance of cell viability. Oncology Reports 30(1): 433-440, 2014