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Cancer and Metastasis Reviews

, Volume 31, Issue 3–4, pp 493–500 | Cite as

Suppression of tumor and metastasis progression through the scaffolding functions of SSeCKS/Gravin/AKAP12

  • Irwin H. Gelman
Article

Abstract

Scaffolding proteins such as SSeCKS/Gravin/AKAP12 (“AKAP12”) are thought to control oncogenic signaling pathways by regulating key mediators in a spatiotemporal manner. The downregulation of AKAP12 in many human cancers, often associated with promoter hypermethylation, or the loss of its locus at 6q24-25.2, correlates with progression to malignancy and metastasis. The forced re-expression of AKAP12 in cancer cell lines suppresses in vitro parameters of oncogenic growth, invasiveness, and cell motility through its ability to scaffold protein kinase C (PKC), F-actin, cyclins, Src, and phosphoinositides, and possibly through additional scaffolding domains for PKA, calmodulin, β1,4-galactosyltransferase-polypeptide-1, β2-adrenergic receptors, and cAMP-specific 3′,5′-cyclic phosphodiesterase 4D. Moreover, AKAP12 re-expression in tumor models results in metastasis suppression through the inhibition of Src-regulated, VEGF-mediated neovascularization at distal sites. The current review will describe the emerging understanding of how AKAP12 regulates cellular senescence and oncogenic progression at the level of tumor cells and tumor-associated microenvironment via its multiple scaffolding functions.

Keywords

SSeCKS/AKAP12 Metastasis Neovascularization Microenvironment Src PKC PKA Cyclin 

Notes

Acknowledgments

This work is supported by funding from the NIH (CA94108), DOD (PC074228, PC061246, BC086529) and the Roswell Park Alliance Foundation.

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Cancer GeneticsRoswell Park Cancer InstituteBuffaloUSA

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