VIP Induces Snail1, A Master EMT Regulator: Upregulation in A375 Cancer Cells
Abstract
VIP is neurotransmitter with pleiotropic functions in mammals. It is expressed by a large number of tissues, including the CNS, PNS, innate and adaptive immune systems. VIP has two endogenous G-protein coupled receptors, termed VPAC 1 and VPAC2. VIP signaling through VPAC1 receptor has been documented to transactivate EGFR in healthy and cancerous cells leading to the activation of multiple downstream signaling pathways. EGFR signaling is a potent inducer of the master regulator EMT, called Snail1, which is a zinc-finger, transcription factor that is associated with downregulating epithelial markers like E-cadherin, while upregulating mesenchymal markers necessary for invasion and metastasis. We hypothesize that VIP upregulates Snail1expression in cancer cells. Our results showed that VIP treatment of epithelial cells increased Snail1 expression transiently at 1h and 4h then returned to basal levels at 24h. This research has implications in development of targeted therapies for cancer.