Suppression of mTOR complex 2-dependent AKT phosphorylation in melanoma cells by combined treatment with rapamycin and LY294002

The British Journal of Dermatology
J WerzowaB Pratscher

Abstract

Inhibition of mTOR complex 1 (mTORC1) with rapamycin leads to phosphorylation of AKT in some cancer cells, with unknown biological consequences. The role of this phosphorylation in melanoma is unknown, although preliminary clinical data indicate poor activity of rapalogues in melanoma. We aimed at elucidating the role of AKT phosphorylation after mTORC1 inhibition in melanoma cells. Western blotting, apoptosis assays, cell cycle analyses and viability assays were performed to analyse the effects of rapamycin and LY294002 treatment on melanoma cells. For suppression of mTOR complex 2 (mTORC2) an siRNA directed against rictor was used. Rapamycin showed limited effects on cell viability but resulted in strong and lasting AKT phosphorylation in melanoma cells. Combined PI3K/mTOR inhibition with LY294002 had pronounced effects on viability but also led to increased AKT phosphorylation after prolonged treatment. In contrast, combination of rapamycin plus LY294002 suppressed AKT phosphorylation. Suppression of AKT phosphorylation did not correlate with decreases in cell viability. Inhibition of mTORC2 led to reduced levels of phosphorylated AKT. mTORC1 inhibition with rapamycin and with LY294002 can lead to AKT phosphorylation in mela...Continue Reading

References

Sep 9, 2000·Journal of Medical Genetics·J T CelebiM Peacocke
Nov 1, 2000·Cell·T Schmelzle, M N Hall
Aug 16, 2001·Proceedings of the National Academy of Sciences of the United States of America·M S NeshatC L Sawyers
Oct 17, 2002·Dermatologic Clinics·Caroline Bevona, Arthur J Sober
Jun 6, 2003·Oncogene·Heng WuFrank G Haluska
Mar 19, 2004·Nature·Hans-Guido WendelScott W Lowe
May 4, 2004·Nature Reviews. Cancer·Mary-Ann Bjornsti, Peter J Houghton
Jul 14, 2004·The Journal of Cell Biology·Laura S HarringtonRichard F Lamb
Jul 16, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Isabelle Sansal, William R Sellers
Jan 18, 2005·Trends in Biochemical Sciences·Laura S HarringtonRichard F Lamb
Feb 4, 2005·Nature·Joel D Richter, Nahum Sonenberg
Feb 19, 2005·Science·D D SarbassovDavid M Sabatini
Feb 22, 2005·Lancet·John F ThompsonRichard F Kefford
Mar 31, 2005·Journal of the American Chemical Society·Laura A BanaszynskiThomas J Wandless
Apr 6, 2005·The Journal of Biological Chemistry·Siraj M Ali, David M Sabatini
Apr 21, 2005·The Journal of Clinical Investigation·Yakov ChudnovskyAmy E Adams
Jun 14, 2005·Lancet·Spyros Retsas
Jun 14, 2005·Lancet·Vincenzo de GiorgiPaolo Carli
Jun 23, 2005·Frontiers in Bioscience : a Journal and Virtual Library·Friedegund MeierMeenhard Herlyn
Jul 15, 2005·American Journal of Physiology. Endocrinology and Metabolism·Lily Q Dong, Feng Liu
Sep 20, 2005·Cancer Cell·Nissim Hay
Oct 14, 2005·The Journal of Biological Chemistry·Richard C Hresko, Mike Mueckler
Nov 17, 2005·Oncogene·Davide Ruggero, Nahum Sonenberg
Dec 13, 2005·Nature Reviews. Cancer·Andreas G BaderPeter K Vogt
Feb 3, 2006·Cancer Research·Kathryn E O'ReillyNeal Rosen
Feb 14, 2006·Cell·Stephan WullschlegerMichael N Hall
Apr 11, 2006·Molecular Cell·Dos D SarbassovDavid M Sabatini
Apr 14, 2006·Mayo Clinic Proceedings·Deborah L CumminsArjun Chanmugam
May 16, 2006·Cancer Cell·Qi-Wen FanWilliam A Weiss
Aug 23, 2006·Biochemistry·Marilisa LeoneMaurizio Pellecchia
Oct 17, 2006·Oncogene·J H Reiling, D M Sabatini
Oct 17, 2006·Oncogene·J B Easton, P J Houghton
Oct 21, 2006·Biochemical Society Transactions·P T HawkinsL R Stephens
Feb 17, 2007·The Biochemical Journal·Severine I GharbiMichael D Waterfield
Oct 5, 2007·The Journal of Investigative Dermatology·Magdalena KarbowniczekElizabeth P Henske

❮ Previous
Next ❯

Citations

Apr 3, 2009·Pigment Cell & Melanoma Research·Pablo Lopez-Bergami
Apr 7, 2011·Pigment Cell & Melanoma Research·Lauretta LevatiStefania D'Atri
Oct 15, 2011·Pigment Cell & Melanoma Research·Agnieszka Checinska, María S Soengas
Dec 21, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Saadia A AzizHarriet M Kluger
Jan 5, 2012·Dermatology Research and Practice·Felipe Ades, Otto Metzger-Filho
Nov 5, 2010·The Journal of Investigative Dermatology·Johannes WerzowaVolker Wacheck
May 25, 2012·Expert Opinion on Therapeutic Targets·Helena PópuloJosé Manuel Lopes
Aug 8, 2015·PloS One·Edgardo SalvatierraOsvaldo L Podhajcer
Nov 12, 2016·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Alexey GoltsovJames L Bown
Mar 13, 2012·International Journal of Molecular Sciences·Helena PópuloPaula Soares
Feb 6, 2019·Veterinary and Comparative Oncology·Franziska SchmidBarbara Pratscher
Sep 12, 2015·Oncotarget·Florence LaugierNicolas Dumaz
Jun 15, 2017·International Journal of Cancer. Journal International Du Cancer·Sheema AlmozyanHazem Ghebeh
Apr 24, 2010·The British Journal of Dermatology·A B AlexandroffG A Johnston
Jun 30, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thorsten FuerederVolker Wacheck
Oct 14, 2010·Cancer Research·Kerri L ChockWael M ElShamy
Apr 28, 2019·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Fathi EmhemmedGuy Fuhrmann

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.