Characterization of TRIP6-dependent nasopharyngeal cancer cell migration

Abstract

Nasopharyngeal carcinoma (NPC) is a leading malignancy most often reported in endemic areas such as in Southeast Asia and the Mediterranean area. NPC remains as a major challenge for clinical management largely due to its high propensity for cancer invasion, metastasis, and recurrence. Therefore, control of NPC cell motility stands as a major obstacle for successful NPC management. The current study sought to identify a new regulator for NPC cell motility in light of previous data showing a similar role of thyroid receptor interactor protein 6 (TRIP6) in other cancer cell types. Results showed that TRIP6 is up-regulated in NPC cells as compared to normal nasopharyngeal epithelial cells. Moreover, TRIP6 overexpression/knockdown results in significant enhancement/inhibition of NPC cell migration, respectively. Interestingly, data also suggested that TRIP6 Y55E (tyrosine 55 to glutamic acid) mutant can promote cell migration more efficiently than wild type does, while Y55A (tyrosine 55 to alanine) mutant has no effects on cell migration as demonstrated with different methodology. Consistently, we also found that c-Src physically interacts with TRIP6, which suggests its potential role as a TRIP6 kinase. Taken together, these data suggested that TRIP6 is involved in the regulation of NPC cell motility, and phosphorylation of tyrosine 55 residue plays an important regulatory role for this event. These data highlight the importance of TRIP6 as a novel regulator of NPC cell motility, which warrants a good basis for further investigation on the underlying mechanism by which TRIP6 exerts this effect and the pathophysiological role TRIP6 plays in vivo.