GABAB1e promotes the malignancy of human cancer cells by targeting the tyrosine phosphatase PTPN12
Bo Wei, Yini Zhu, Peng Yang, Yong Han, Suyun Wang, Xiaomei Wang, Shuai Xia, Xiaoguang Song, Zhongling Zhang, Sheng Wang, Philippe Rondard, Jean-Philippe Pin, Xinnong Jiang, Jianfeng Liu
Journal：iScience
IF：5.46
DOI：10.1016/j.isci.2021.103311
PMID：34778730
Published：2021-10-16
research field：神经科学药理学遗传学病理学分子医学
Abstract
Summary Neurotransmitter receptors are involved in cancer progression. Among them, the heterodimeric GABA B receptor, activated by the main inhibitory neurotransmitter GABA, is composed of the transmembrane GABA B1 and GABA B2 subunits. The oncogenic role of the isoform GABA B1e (GB 1e ) containing only the extracellular domain of GABA B1 remains unclear. We revealed that GB 1e is largely expressed in human breast cancer (BrCa) cell lines as well as in BrCa tissues where it is upregulated. Moreover, GB 1e promoted the malignancy of BrCa cells both in vitro and in vivo . We propose that GB 1e favors EGFR signaling by interacting with PTPN12 to disrupt the interaction between EGFR and PTPN12, and phosphorylation of Y230 and Y404 on GB 1e is required in this process. Our data highlight that the GABBR1 gene through the expression of the GB 1e isoform might play an important oncogenic role in BrCa and that GB 1e is of interest for the treatment of some cancers.
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