The Ins and Outs of Survivin

Tue, 09/03/2019 - 08:40

Exosomes arise from the late endosomal compartment through inward budding of multivesicular bodies and may contain multiple proteins, lipids, DNA, RNAs and biomolecules of viruses/prions.

By Rachel M.A. Linger, Ph.D.

What is survivin?

Survivin is a small (16.5 kDa) protein normally found in human fetal tissue. In contrast, survivin is typically undetectable in most normal adult tissues. Expression of survivin occurs in several subcellular locations including the cytoplasm, nucleus, mitochondria, and cytoskeleton1. As its name implies, survivin negatively regulates apoptosis, thus promoting proliferation and survival. Indeed, it is a member of the inhibitor of apoptosis (IAP) protein family.

IAP Family of proteins, Caspase Inhibitors

Class 1

XIAP (Caspase 3, 7, 9)
cIAP (Caspase 3, 7)
ILP2 (Caspase 9)
ML-IAP (Caspase 3, 9)

Class 2

NAIP (Caspase 3, 7)

Class 3

SURVIVIN (Caspase 3, 7)

Like other IAPs, survivin blocks apoptosis through direct interaction with cytoplasmic caspases, including effector caspases 3 and 7, which serve as a point of convergence for the intrinsic and extrinsic pathways of apoptosis2. Additional intracellular functions of survivin have been elucidated including regulation of mitosis and cytokinesis, functions associated with cytoskeletal localization of survivin during the G2/M-phase of the cell cycle1. Given these roles in cell division, proliferation, and survival, it is not surprising that survivin is ubiquitously expressed in many types of cancer cells, where its presence correlates with tumor progression, resistance to therapy, and poor prognosis2.

Survivin, a member of the IAP-Inhibitor of Apoptosis-proteins, is involved in the regulation of cell division steps including sister chromatid segregation, mitotic spindle assembly checkpoint, and cytokinesis.Immunocytochemistry/Immunofluorescence: Survivin Antibody [NB500-201] - Staining of Telophase with accumulation of survivin in the midbodies of two daughter cells.

New survivin cellular function

In addition to the intracellular roles described above, it was discovered that survivin is secreted from cancer cells via exosomes3. This extracellular population of exosomal survivin has been shown to promote proliferation of neighboring cancer cells and facilitate tumor cell invasion. In a recent publication, Gonda et al   . hypothesized that survivin is taken up by cancer cells via receptor-mediated endocytosis4. They utilized an antibody blocking technique to demonstrate that diverse types of receptors contribute to uptake of exosomal survivin by HeLa cells. The most robust effects were observed when transferrin receptor 1 was blocked on the surface of the HeLa cells. Blockade of insulin receptor alpha and endothelin B receptor resulted in more modest inhibition of exosome internalization. Additional experiments indicated that exosomal survivin plays a key role in exosome uptake by HeLa cells.

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Significance for targeting survivin in cancer

These findings corroborate earlier studies that identified survivin and transferrin receptor 1 as potential therapeutic targets in a variety of cancer types. Further investigation is warranted to establish a direct link between survivin mediated exosome internalization and tumor progression.

Rachel LingerRachel M.A. Linger, Ph.D.  
Associate Professor of Pharmacology, Rocky Vista University


  1. Wheatley, S. P., & Altieri, D. C. (2019). Survivin at a glance. Journal of Cell Science.
  2. Chen, X., Duan, N., Zhang, C., & Zhang, W. (2016). Survivin and tumorigenesis: Molecular mechanisms and therapeutic strategies. Journal of Cancer.
  3. Khan, S., Jutzy, J. M. S., Aspe, J. R., McGregor, D. W., Neidigh, J. W., & Wall, N. R. (2011). Survivin is released from cancer cells via exosomes. Apoptosis.
  4. Gonda, A., Kabagwira, J., Senthil, G. N., Bennit, H. R. F., Neidigh, J. W., Khan, S., & Wall, N. R. (2018). Exosomal survivin facilitates vesicle internalization. Oncotarget.


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