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Published in:

01-12-2012

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

Author: Irwin H. Gelman

Published in: Cancer and Metastasis Reviews | Issue 3-4/2012

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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Title: Suppression of tumor and metastasis progression through the scaffolding functions of SSeCKS/Gravin/AKAP12
Author: Irwin H. Gelman
Publication date: 01-12-2012
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 3-4/2012
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-012-9360-1

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