Ras GRP 3, a Ras guanyl releasing protein 3 that contributes to malignant proliferation and aggressiveness in human esophageal squamous cell carcinoma

Summary Esophageal squamous cell carcinoma ( ESCC ) is one of the most common cancers worldwide; however, clinical and pathological parameters have limited ability in discriminating between clinically significant and indolent ESCC . Since Ras GRP 3 transcript levels have prognostic value in discriminating ESCC with different clinical aggressiveness, we decided to investigate its putative oncogenic role in ESCC . We found that Ras GRP 3 was highly expressed in ESCC cells. Suppression of endogenous Ras GRP 3 expression in esophageal cell lines reduced Ras‐ GTP formation as well as AKT phosphorylation. Ras GRP 3 suppression also inhibited cell invasion and migration and reduced proliferation, demonstrating the importance of Ras GRP 3 for the transformed phenotype of melanoma cells. Suppression of Ras GRP 3 expression in these cells inhibited downstream Ras GRP 3 responses and suppressed cell growth and migration, confirming the functional role of Ras GRP 3 in the altered behaviour of these cells. This suggests that Ras GRP 3 may function as a Ras activator in the phosphoinositide signalling pathway and may potentially serve as a new therapeutic target.