Cancer and Metastasis Reviews

, Volume 37, Issue 4, pp 665–676 | Cite as

Pleiotropic effects of moonlighting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in cancer progression, invasiveness, and metastases

  • Michael A. SiroverEmail author


Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) may represent the quintessential example of a moonlighting protein. The latter are a new, intriguing class of cell proteins which exhibit multiple activities in different subcellular locales apart from their initially, well-characterized function. As such, apart from its classical role in energy production, membrane-bound GAPDH is required for membrane fusion, endocytosis and, intriguingly, for iron transport. Cytoplasmic GAPDH regulates mRNA stability and is required for ER to Golgi trafficking. Nuclear GAPDH is involved in apoptosis, transcriptional gene regulation, the maintenance of DNA integrity, as well as nuclear tRNA export. Paradoxically, the etiology of a number of human pathologies is dependent upon GAPDH structure and function. In particular, recent evidence indicates a significant role for moonlighting GAPDH in tumorigenesis. Specifically, these include its role in the survival of tumor cells, in tumor angiogenesis, as well as its control of tumor cell gene expression and posttranscriptional regulation of tumor cell mRNA. Each of these activities correlates with increased tumor progression and, unfortunately, a poor prognosis for the afflicted individual.


Glyceraldehyde-3-phosphate dehydrogenase Tumorigenesis Apoptosis Cancer angiogenesis Posttranscriptional mRNA regulation Cancer gene expression 


Funding information

Work in the author’s laboratory was funded by grants from the National Institutes of Health, the National Science Foundation, and by the W.W. Smith Charitable Trust.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmacology, The Lewis Katz School of MedicineTemple UniversityPhiladelphiaUSA

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