摘要：SummaryNeurotransmitter receptors are involved in cancer progression. Among them, the heterodimeric GABABreceptor, activated by the main inhibitory neurotransmitter GABA, is composed of the transmembrane GABAB1and GABAB2subunits. The oncogenic role of the isoform GABAB1e(GB1e) containing only the extracellular domain of GABAB1remains unclear. We revealed that GB1eis largely expressed in human breast cancer (BrCa) cell lines as well as in BrCa tissues where it is upregulated. Moreover, GB1epromoted the malignancy of BrCa cells bothin vitroandin vivo. We propose that GB1efavors EGFR signaling by interacting with PTPN12 to disrupt the interaction between EGFR and PTPN12, and phosphorylation of Y230 and Y404 on GB1eis required in this process. Our data highlight that theGABBR1gene through the expression of the GB1eisoform might play an important oncogenic role in BrCa and that GB1eis of interest for the treatment of some cancers.Graphical abstractDisplay OmittedHighlights•GABAB1epromotes the malignancy of breast cancer cells bothin vitroandin vivo•Specific phosphorylation of GABAB1eis critical for its association with PTPN12•GABAB1edisrupts EGFR interacting with PTPN12 and induces EGFR-PI3K/Akt signalingBiological sciences; Molecular biology; Neuroscience
