Human granulocytes express a variety of nonspecific cross-reacting antigens (NCA). These proteins are glycoproteins and belong to the carcinoembryonic antigen (CEA) family. NCAs have been identified in a variety of normal and cancerous epithelial cells and also in hematopoietic cells including granulocytes and monocytes NCA-90 in tumors correlates inversely with cellular differentiation and is an independent prognostic factor associated with a higher risk of colorectal cancer relapse. NCA-90 is also an important protein associated with cell adhesion; its expression on neutrophils is involved in adhesion to cytokine-activated endothelial cells. This molecule correlates with other members of the CEA family with homotypic and heterotypic interactions.
NCA-90 inhibits anoikis, a form of programmed cell death that occurred in anchorage-dependent cells. The modulation of NCA-90 expression alters the malignant phenotype of cancer cells. The disruption of the NCA-90 gene down-regulates the Akt cell survival pathway. In addition, deficiency of NCA-90 enhances cell anoikis, increases caspase activation in response to anchorage-independent conditions, and inhibits metastasis in vivo. Expression of this membrane protein is also associated with increased invasiveness through a c-src-dependent mechanism. Thus, NCA-90 may represent a therapeutic target to control malignancy and/or metastasis.
For Research Use Only. NOT FOR CLINICAL USE.
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