Wild type, dEX3 and 2B survivin isoforms localize to the tumor cell plasma membrane, are secreted in exosomes, and interact with extracellular tubulin

Sheila Figel; Meaghan Birkemeier; Sanam Sahjram Dharma; Tara Barone; Emma Steinmetz; Michael Ciesielski; Robert Fenstermaker

doi:10.1016/j.bbrep.2021.101174

Wild type, dEX3 and 2B survivin isoforms localize to the tumor cell plasma membrane, are secreted in exosomes, and interact with extracellular tubulin

Biochem Biophys Rep. 2021 Nov 20:28:101174. doi: 10.1016/j.bbrep.2021.101174. eCollection 2021 Dec.

Authors

Sheila Figel¹, Meaghan Birkemeier¹, Sanam Sahjram Dharma², Tara Barone¹, Emma Steinmetz¹, Michael Ciesielski^{1

3

4}, Robert Fenstermaker^{1

3

4}

Affiliations

¹ Department of Neuro Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
² Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
³ Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
⁴ MimiVax, LLC, Buffalo, NY, USA.

Abstract

The Inhibitor of Apoptosis Protein survivin (svn) is upregulated in nearly all types of cancer and represents a promising therapeutic target. Localization to specific subcellular compartments and interactions with various binding partners allow survivin to play diverse roles in apoptosis resistance and mitosis. Survivin has recently been found in two extracellular compartments: the outer plasma membrane and secreted exosomes. In addition to svn-wt, splice variants svn-dEX3 and svn-2B are also overexpressed in human tumors. Here we show that, similarly to svn-wt, svn-dEX3 and svn-2B can be displayed on the outer plasma membrane, and secreted in exosomes. Additionally, we have identified a novel interaction of all three forms of survivin with secreted tubulin.

Keywords: Exosome; Plasma membrane; Survivin; Survivin-2B; Survivin-dEX3; Tubulin.