title: Adaptors for disorders of the brain? The cancer signaling proteins NEDD9, CASS4, and PTK2B in Alzheimer's disease.
abstract: No treatment strategies effectively limit the progression of Alzheimer's disease (AD), a common and debilitating neurodegenerative disorder. The absence of viable treatment options reflects the fact that the pathophysiology and genotypic causes of the disease are not well understood. The advent of genome-wide association studies (GWAS) has made it possible to broadly investigate genotypic alterations driving phenotypic occurrences. Recent studies have associated single nucleotide polymorphisms (SNPs) in two paralogous scaffolding proteins, NEDD9 and CASS4, and the kinase PTK2B, with susceptibility to late-onset AD (LOAD). Intriguingly, NEDD9, CASS4, and PTK2B have been much studied as interacting partners regulating oncogenesis and metastasis, and all three are known to be active in the brain during development and in cancer. However, to date, the majority of studies of these proteins have emphasized their roles in the directly cancer relevant processes of migration and survival signaling. We here discuss evidence for roles of NEDD9, CASS4 and PTK2B in additional processes, including hypoxia, vascular changes, inflammation, microtubule stabilization and calcium signaling, as potentially relevant to the pathogenesis of LOAD. Reciprocally, these functions can better inform our understanding of the action of NEDD9, CASS4 and PTK2B in cancer.
authors.affiliation: Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA ; Program in Molecular and Cell Biology and Genetics, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Tim N
authors.initials: TN
authors.lastname: Beck
authors.affiliation: Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Nicolas
authors.affiliation: Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA ; Program in Molecular and Cell Biology and Genetics, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Meghan C
authors.initials: MC
authors.lastname: Kopp
authors.affiliation: Developmental Therapeutics Program, Fox Chase Cancer Center, Philadelphia, PA, USA ; Program in Molecular and Cell Biology and Genetics, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Erica A
authors.initials: EA
authors.lastname: Golemis
keywords: APP; Alzheimer's disease; Amyloid; Brain; CAK-β; CAS; CASS4; Cancer; HEF1; HEPL; NEDD9; Neurodegenerative; PSEN1; PSEN2; PTK2B; PYK2; RAFTK; Tau