AbstractsBiology & Animal Science

Neuroendocrine differentiation (NED) in prostate cancer cells has recently gained increased attention, as NED has been shown to have roles in the development of prostate cancer, as well as being correlated to poor prognosis and survival. The mechanisms regulating NED in prostate cancer cells are unclear, but β2-Adrenergic Receptor (β2AR) dependent increase of intracellular cAMP and MAPK activation have been implicated as potent inducers. Here we identify a novel transmembrane interactor of β2AR, the six transmembrane protein STAMP1, previously implicated in prostate cancer progression. We show that STAMP1 physically interacts with mediated knockdown of STAMP1 in LNCaP cells upregulates NED markers NSE and DDC and induces a morphological change in the cells towards a neuroendocrine phenotype. Furthermore, STAMP1 knockdown increases β2AR induced phosphorylation of extracellular regulated kinase (ERK1/2) consistent with the relief of β2AR repression. Consistently, expression data from prostate cancer tissue samples show an inverse correlation between STAMP1 and the NED marker NSE. In addition, in vitro invasion of LNCaP cells is decreased upon β2AR activation, mediated in part by reduced MMP7 expression, and this effect is mimicked by loss of STAMP1. These observations suggest that STAMP1 plays an important role in downregulating β2AR signaling, involved in NED and invasion in prostate cancer.