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

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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.

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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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  1. Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA

    Irwin H. Gelman

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Gelman, I.H. Suppression of tumor and metastasis progression through the scaffolding functions of SSeCKS/Gravin/AKAP12. Cancer Metastasis Rev 31, 493–500 (2012). https://doi.org/10.1007/s10555-012-9360-1

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