Novel strategies to target the survivin pathway in cancer – interference with nuclear export prevents the tumor promoting activites of survivin : meeting abstract

  • 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.

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Author:Shirley Knauer, Shirley K. Knauer, Oliver Holger Krämer, Thomas Knösel, Knut Engels, Franz RödelORCiDGND, Jürgen BriegerORCiDGND, Wolf Mann, Negusse Habtemichael, Ivar Petersen, Thorsten Heinzel, Roland Stauber
Parent Title (German):27. Deutscher Krebskongress. Berlin, 22.-26.03.2006
Publisher:German Medical Science
Place of publication:Düsseldorf ; Köln
Document Type:Conference Proceeding
Year of Completion:2006
Date of first Publication:2006/03/20
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2007/06/08
Page Number:3
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.
Source:27. Deutscher Krebskongress, Deutsche Krebsgesellschaft e.V. : 22. bis 26.03.2006, Berlin. Düsseldorf {[u.a.] : German Medical Science; Doc PO495
Institutes:Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung-Nicht kommerziell-Keine Bearbeitung 3.0