Neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9) (NEDD9)

Neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), also known as HEF1 or Cas-L, is a multi-domain scaffolding protein belonging to the Crk-associated substrate (CAS) family (UniProt: Q14511). It acts as a critical signaling hub at focal adhesions, where it integrates signals from the extracellular matrix to regulate cell adhesion, migration, and invasion (PubMed: 25236394). NEDD9 is frequently overexpressed in various malignancies, including melanoma, breast cancer, and glioblastoma, where it promotes the epithelial-mesenchymal transition (EMT) and metastatic dissemination (PubMed: 21725356). Because NEDD9 lacks intrinsic enzymatic activity, it is considered a challenging target for traditional small-molecule inhibitors. Consequently, therapeutic strategies often focus on NEDD9 mRNA, utilizing RNA interference (RNAi) or antisense oligonucleotides (ASOs) to downregulate protein expression and disrupt pro-invasive signaling pathways (PubMed: 28651314). Beyond its role in oncology, NEDD9 has been implicated in the pathogenesis of polycystic kidney disease and vascular disorders (PubMed: 24108473). Targeting NEDD9 mRNA offers a promising approach to inhibit the metastatic cascade in aggressive cancers.

Other names

HEF1Cas-LCASLCASS2Human enhancer of filamentation 1Crk-associated substrate-related protein of lymphocytes

Inhibition of NEDD9 protein expression through RNA interference or antisense-mediated degradation of NEDD9 mRNA, leading to the disruption of pro-metastatic focal adhesion signaling.