English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.Recent evidence shows that lipid raft membrane domains modulate both cell survival and death. Here, we have found that the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway is present in the lipid rafts of mantle cell lymphoma (MCL) cells, and this location seems to be critical for full activation and MCL cell survival. The antitumor lipids (ATLs) edelfosine and perifosine target rafts, and we found that ATLs exerted in vitro and in vivo antitumor activity against MCL cells by displacing Akt as well as key regulatory kinases p-PDK1 (phosphatidylinositol-dependent protein kinase 1), PI3K and mTOR (mammalian TOR) from lipid rafts. This raft reorganization led to Akt dephosphorylation, while proapoptotic Fas/CD95 death receptor was recruited into rafts. Raft integrity was critical for Ser473 Akt phosphorylation. ATL-induced apoptosis appeared to correlate with the basal Akt phosphorylation status in MCL cell lines and primary cultures, and could be potentiated by the PI3K inhibitor wortmannin, or inhibited by the Akt activator pervanadate. Classical Akt inhibitors induced apoptosis in MCL cells. Microenvironmental stimuli, such as CD40 ligation or stromal cell contact, did not prevent ATL-induced apoptosis in MCL cell lines and patient-derived cells. These results highlight the role of raft-mediated PI3K/Akt signaling in MCL cell survival and chemotherapy, thus becoming a new target for MCL treatment. © 2013 Macmillan Publishers Limited.This work was supported by grants from Ministerio de Economía y Competitividad of Spain (SAF2008-02251 and SAF2011-30518 to FM; SAF2009-09503 to DC), Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, cofunded by the Fondo Europeo de Desarrollo Regional of the European Union (RD06/0020/1037 and RD12/0036/0065 to FM; RD06/0020/0014 to DC), Fondo de Investigación Sanitaria and European Commission, Instituto de Salud Carlos III (PI09/0060 to GR; PS09/01915 to CG), European Community’s Seventh Framework Programme FP7-2007-2013 (grant HEALTH-F2-2011-256986, PANACREAS to FM), Junta de Castilla y León (CSI052A11-2 and CSI221A12-2 to FM; Biomedicine Project 2010–2011 to CG) and Generalitat de Catalunya (2009SGR967 to DC). MRS was recipient of a predoctoral fellowship from the Fundaçâo para a Ciência e Tecnologia (Ministério da Ciencia, Tecnología e Ensino Superior of Portugal), and AM was a recipient of a predoctoral fellowship from IDIBAPS. CG was supported by the Ramón y Cajal Program from the Ministerio de Ciencia e Innovación of Spain.Peer Reviewe

Lipid raft-mediated Akt signaling as a therapeutic target in mantle cell lymphoma