Preclinical and clinical studies of the NEDD9 scaffold protein in cancer and other diseases

• Published in: Gene Vol. 567; no. 1; pp. 1 - 11
• Main Authors: Shagisultanova, Elena, Gaponova, Anna V., Gabbasov, Rashid, Nicolas, Emmanuelle, Golemis, Erica A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2015
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - physiology; CAS family protein; CAS-L; HEF1; Human malignancy; Humans; NEDD9; Neoplasms - genetics; Phosphoproteins - genetics; Phosphoproteins - physiology; Polycystic Kidney Diseases - genetics; Prognosis; Protein function; Signal transduction; Stroke - genetics; ALL; FOXC1; Prognosis; RARE; IHC; RTK; HEF1; NEDD9; RXR; HDAC6; AURKA; Signal transduction; ADPKD; TGF-beta; shRNA; Protein function; CAS family protein; GIST; CML; Human malignancy; HIF; NSCLC; GEF; HCC; siRNA; EMT; ER; FAK; MMP; CAS; HTLV; miR; CAS-L; CRK; MET
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2015.04.086

Cancer progression requires a significant reprogramming of cellular signaling to support the essential tumor-specific processes that include hyperproliferation, invasion (for solid tumors) and survival of metastatic colonies. NEDD9 (also known as CasL and HEF1) encodes a multi-domain scaffolding protein that assembles signaling complexes regulating multiple cellular processes relevant to cancer. These include responsiveness to signals emanating from the T and B cell receptors, integrins, chemokine receptors, and receptor tyrosine kinases, as well as cytoplasmic oncogenes such as BCR-ABL and FAK- and SRC-family kinases. Downstream, NEDD9 regulation of partners including CRKL, WAVE, PI3K/AKT, ERK, E-cadherin, Aurora-A (AURKA), HDAC6, and others allow NEDD9 to influence functions as pleiotropic as migration, invasion, survival, ciliary resorption, and mitosis. In this review, we summarize a growing body of preclinical and clinical data that indicate that while NEDD9 is itself non-oncogenic, changes in expression of NEDD9 (most commonly elevation of expression) are common features of tumors, and directly impact tumor aggressiveness, metastasis, and response to at least some targeted agents inhibiting NEDD9-interacting proteins. These data strongly support the relevance of further development of NEDD9 as a biomarker for therapeutic resistance. Finally, we briefly discuss emerging evidence supporting involvement of NEDD9 in additional pathological conditions, including stroke and polycystic kidney disease. •The NEDD9 scaffold protein assembles protein complexes that drive tumorigenesis.•NEDD9 signaling supports invasion, survival, ciliary resorption, and mitosis.•NEDD9 expression influences tumor metastasis and therapeutic response.•NEDD9 is a promising biomarker for therapeutic resistance.