The human Nod-like receptor (NLR) protein NOD1 is a well described pattern-recognition receptor with diverse functions. NOD1 is associated with F-actin and its protein levels are upregulated in metastatic cancer cells. A hallmark of cancer cells is their ability to migrate, which involves actin remodelling. Using chemotaxis and wound healing assays, we show that NOD1 expression correlated with the migration rate and chemotactic index in the cervical carcinoma cell line HeLa. The effect of NOD1 in cell migration was independent of NF-?B activity. Co-immunoprecipitation assays identified HCLS1 associated protein X-1 (HAX-1) as a novel interaction partner of NOD1. Silencing of HAX-1 expression reduced the migration behaviour to similar levels as NOD1 knockdown and simultaneous knockdown of NOD1 and HAX-1 showed no additive effect, suggesting that both proteins act in the same pathway.
In conclusion, our data revealed an important role of the pattern-recognition receptor NOD1 in regulating cell migration as well as chemotaxis in human cervical cancer cells and identified HAX-1 as a novel protein interacting with NOD1 involved in this signalling pathway.