Newly Identified Cancer-Associated Role of Human Neuronal Growth Regulator 1 (NEGR1)

Neuronal growth regulator 1 (NEGR1) has become a great interest based on the recent findings that its genetic alteration is implicated in human obesity and human dyslexia. By analyzing the gene expression profiles of tumor biopsies and normal tissues, we identified NEGR1 as a commonly down-regulated gene in many types of human cancer tissues. NEGR1 contains a C-terminal GPI anchor attachment site and is primarily localized to cell membrane rafts, especially in cell-to-cell contacting areas. The oncogenic phenotype was clearly attenuated when NEGR1 was overexpressed in the human ovarian cancer cell line SKOV-3. Furthermore, cell aggregation and neurite outgrowth was greatly increased by NEGR1 overexpression. On the contrary, cell migration and invasion was increased in NEGR1-depleted cells, suggesting that NEGR1 may contribute to tumor suppression. Taken together, we suggest that NEGR1 is a raft-associated extracellular protein that may participate in cell recognition and interaction, which is important in growth control and malignant transformation.