TY  - CONF
A1  - Knauer, Shirley
A1  - Knauer, Shirley K.
A1  - Krämer, Oliver Holger
A1  - Knösel, Thomas
A1  - Engels, Knut
A1  - Rödel, Franz
A1  - Brieger, Jürgen
A1  - Mann, Wolf
A1  - Habtemichael, Negusse
A1  - Petersen, Ivar
A1  - Heinzel, Thorsten
A1  - Stauber, Roland
T1  - Novel strategies to target the survivin pathway in cancer – interference with nuclear export prevents the tumor promoting activites of survivin : meeting abstract
T2  - 27. Deutscher Krebskongress. Berlin, 22.-26.03.2006
N2  - Survivin functions as an apoptosis inhibitor and a regulator of cell division during development and tumorigenesis. Since survivin is a highly relevant target for tumor therapy, we investigated whether interference with it’s dynamic cellular localization represents a novel strategy to inhibit survivin’s cancer promoting functions. We confirmed survivin overexpression in head and neck as well as in colorectal cancers and identified an evolutionary conserved Crm1-dependent nuclear export signal (NES) in survivin. Importantly, nuclear export was required for survivin mediated protection against chemo- and radiotherapy-induced apoptosis by securing efficient interference with cytoplasmic caspases. In dividing cells, the NES was required for tethering of survivin and of the survivin/Aurora-B kinase complex to the mitotic machinery, which was inevitable for proper cell division. The clinical relevance of our findings was supported by showing that preferential nuclear localization of survivin correlated with enhanced survival in a cohort of colorectal cancer patients. Targeting survivin’s nuclear export by the application of NES-specific antibodies promoted its nuclear accumulation and inhibited its cytoprotective function. We here show that nuclear export is essential for the tumor promoting activities of survivin and encourage the identification of chemical inhibitors to specifically interfere with survivin’s nuclear export as a novel class of anticancer therapeutics.
Y1  - 2006
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/1002
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-44787
UR  - http://www.egms.de/en/meetings/dkk2006/06dkk605.shtml
N1  - This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.
IS  - DocPO495
PB  - German Medical Science
CY  - Düsseldorf ; Köln
ER  -