Journal
CANCER AND METASTASIS REVIEWS
Volume 31, Issue 3-4, Pages 493-500Publisher
SPRINGER
DOI: 10.1007/s10555-012-9360-1
Keywords
SSeCKS/AKAP12; Metastasis; Neovascularization; Microenvironment; Src; PKC; PKA; Cyclin
Categories
Funding
- NIH [CA94108]
- DOD [PC074228, PC061246, BC086529]
- Roswell Park Alliance Foundation
Ask authors/readers for more resources
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, beta 1,4-galactosyltransferase-polypeptide-1, beta 2-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available