Akt3-mediated resistance to apoptosis in B-RAF-targeted melanoma cells.

Cancer Research
Y Shao, A E Aplin

Abstract

Melanoma cells are highly resistant to anoikis, a form of apoptosis induced in nonadherent/inappropriate adhesion conditions. Depleting B-RAF or the prosurvival Bcl-2 family protein Mcl-1 renders mutant B-RAF melanoma cells susceptible to anoikis. In this study, we examined the effect of targeting B-RAF on the survival of primary stage melanoma cells cultured in three-dimensional type I collagen gels, which partially mimics the dermal microenvironment. Depletion/inhibition of B-RAF with small interfering RNA or the mutant B-RAF inhibitor, PLX4720, induced apoptosis of mutant B-RAF melanoma cells in three-dimensional collagen. Apoptosis was dependent on two upregulated BH3-only proteins, Bim-EL and Bmf, and was inhibited by ectopic Mcl-1 expression. Akt3 activation has been associated with the survival of melanoma cells. Mutant B-RAF melanoma cells ectopically expressing a constitutively activated form of Akt3 or endogenously expressing mutant Akt3 were protected from apoptosis induced by B-RAF knockdown or PLX4720 treatment. Furthermore, intrinsically resistant metastatic melanoma cells displayed elevated Akt phosphorylation in three-dimensional collagen and were rendered susceptible to PLX4720 by Akt3 knockdown. Importantly, m...Continue Reading

References

Oct 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·O W PetersenM J Bissell
Dec 1, 1992·The Journal of Investigative Dermatology·G ScottJ B McCarthy
Feb 1, 1994·The Journal of Cell Biology·S M Frisch, H Francis
Aug 16, 2000·Proceedings of the National Academy of Sciences of the United States of America·P HenrietY A DeClerck
Nov 27, 2001·Science·E CukiermanK M Yamada
May 4, 2002·Nature Reviews. Molecular Cell Biology·James J TomasekRobert A Brown
May 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marie StahlRené H Medema
Jun 18, 2002·Nature·Helen DaviesP Andrew Futreal
May 27, 2003·Journal of Cell Science·Karen L Schmeichel, Mina J Bissell
Jun 6, 2003·The Journal of Investigative Dermatology·Christiane ThallingerBurkhard Jansen
Jul 5, 2003·Nature Cell Biology·Mauricio J ReginatoJoan S Brugge
Apr 3, 2004·Cancer Research·Claudia WellbrockRichard Marais
Jun 23, 2004·Oncogene·Maria KarasaridesRichard Marais
Oct 7, 2004·Cancer Research·Jill M StahlGavin P Robertson
Mar 21, 2006·Oncogene·K Boisvert-Adamo, A E Aplin
Oct 5, 2006·Cancer Research·Jian-Zhong QinBrian J Nickoloff
Feb 24, 2007·The Journal of Clinical Investigation·Baskaran GovindarajanJack L Arbiser
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Tobias SchmelzleJoan S Brugge
Apr 19, 2007·Cancer Research·SubbaRao V MadhunapantulaGavin P Robertson
Nov 10, 2007·The Journal of Biological Chemistry·David J PankaJames W Mier
Dec 22, 2007·Nature Reviews. Molecular Cell Biology·Richard J Youle, Andreas Strasser
Feb 5, 2008·Oncogene·K Boisvert-Adamo, A E Aplin
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·James TsaiGideon Bollag
May 3, 2008·Cancer Research·Mitchell CheungGavin P Robertson
Aug 22, 2008·Pigment Cell & Melanoma Research·Robert A CartlidgeMartin McMahon
Sep 25, 2008·British Journal of Cancer·M A DaviesG B Mills
Mar 14, 2009·Nature Genetics·David DankortMarcus Bosenberg
Apr 18, 2009·Molecular Cancer Research : MCR·Karen Boisvert-AdamoAndrew E Aplin
Jul 25, 2009·Pigment Cell & Melanoma Research·Vernon K Sondak, Keiran Smalley
Aug 5, 2009·The Journal of Cell Biology·Delphine MérinoPhilippe Bouillet
Aug 18, 2009·Pigment Cell & Melanoma Research·Leisl M PackerRichard Marais
Feb 13, 2013·Clinical and Experimental Dermatology·G W M Millington

❮ Previous
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Citations

Aug 4, 2012·Cell Death and Differentiation·Y Shao, A E Aplin
Jan 20, 2012·Cell Death & Disease·Y Shao, A E Aplin
May 29, 2013·Nature Reviews. Clinical Oncology·Geoffrey T GibneyKeiran S M Smalley
Oct 13, 2012·Nature Reviews. Drug Discovery·Gideon BollagPeter Hirth
Oct 19, 2012·The Journal of Biological Chemistry·Fred M KaplanAndrew E Aplin
Apr 5, 2012·Genes & Development·Jeremy S Logue, Deborah K Morrison
May 3, 2012·Genes & Development·Liesbeth C W VredeveldDaniel S Peeper
Dec 2, 2011·Cancer Research·Jessie VillanuevaMeenhard Herlyn
Mar 31, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Adina VulturMeenhard Herlyn
Aug 17, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hwa Jin LeeSuzie Chen
May 4, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Elena TassiAndrea Anichini
Feb 22, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kim H T ParaisoKeiran S M Smalley
Mar 4, 2011·Cancer Prevention Research·Chin-Ying ChungGavin P Robertson
Nov 23, 2012·Cancer Discovery·Ophélia MaertensKaren Cichowski
Apr 2, 2013·The Journal of Clinical Investigation·Ethan V AbelAndrew E Aplin
Mar 2, 2013·Therapeutic Advances in Medical Oncology·Muhammad KhattakJames Larkin
May 23, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lisa ZimmerDirk Schadendorf
Jan 10, 2013·PloS One·Adoración Martínez-PalaciánAránzazu Sánchez
Jun 6, 2014·International Journal of Oncology·Angela RussoMassimo Libra
Apr 17, 2014·Journal of Carcinogenesis·Anthony Jarkowski, Nikhil I Khushalani
May 29, 2014·The Journal of Clinical Investigation·Jamie N AnastasRandall T Moon
Sep 21, 2013·Journal of the National Cancer Institute·Christopher H LieuS Gail Eckhardt
Oct 1, 2013·Expert Opinion on Emerging Drugs·Francesco SabbatinoCristina R Ferrone
Mar 5, 2015·Proceedings of the National Academy of Sciences of the United States of America·Kristen M TurnerWei Zhang
Jul 18, 2012·Dermatologic Clinics·Sunandana Chandra, Anna C Pavlick
Dec 15, 2011·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Yingfang TianFrank R Sharp
Oct 11, 2013·The Journal of Investigative Dermatology·Edward HartsoughAndrew E Aplin
Mar 10, 2015·The Journal of Investigative Dermatology·Yongping ShaoAndrew E Aplin
May 20, 2011·The Journal of Investigative Dermatology·Andrew E AplinYongping Shao
May 8, 2015·The Journal of Investigative Dermatology·Nabanita MukherjeeYiqun G Shellman

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