Wei Bo, Zhu Yini, Yang Peng, Han Yong, Wang Suyun, Wang Xiaomei, Xia Shuai, Song Xiaoguang, Zhang Zhongling, Wang Sheng, Rondard Philippe, Pin Jean-Philippe, Jiang Xinnong, Liu Jianfeng
Key Laboratory of Molecular Biophysics of MOE, International Research Center for Sensory Biology and Technology of MOST, College of Life Science and Technology, Huazhong University of Science and Technology (HUST), Wuhan 430074, China.
Department of Breast & Endocrine Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, China.
iScience. 2021 Oct 16;24(11):103311. doi: 10.1016/j.isci.2021.103311. eCollection 2021 Nov 19.
Neurotransmitter receptors are involved in cancer progression. Among them, the heterodimeric GABA receptor, activated by the main inhibitory neurotransmitter GABA, is composed of the transmembrane GABA and GABA subunits. The oncogenic role of the isoform GABA (GB) containing only the extracellular domain of GABA remains unclear. We revealed that GB is largely expressed in human breast cancer (BrCa) cell lines as well as in BrCa tissues where it is upregulated. Moreover, GB promoted the malignancy of BrCa cells both and . We propose that GB favors EGFR signaling by interacting with PTPN12 to disrupt the interaction between EGFR and PTPN12, and phosphorylation of Y230 and Y404 on GB is required in this process. Our data highlight that the gene through the expression of the GB isoform might play an important oncogenic role in BrCa and that GB is of interest for the treatment of some cancers.
神经递质受体参与癌症进展。其中，由主要抑制性神经递质γ-氨基丁酸（GABA）激活的异二聚体GABA受体，由跨膜的GABAα和GABAβ亚基组成。仅包含GABAα胞外域的亚型GABAα（GB）的致癌作用仍不清楚。我们发现GB在人乳腺癌（BrCa）细胞系以及上调的BrCa组织中大量表达。此外，GB在体内和体外均促进了BrCa细胞的恶性肿瘤形成。我们提出GB通过与PTPN12相互作用来破坏EGFR与PTPN12之间的相互作用，从而有利于EGFR信号传导，并且在此过程中GB上Y230和Y404的磷酸化是必需的。我们的数据突出表明，通过GB亚型的表达，GABRA1基因可能在BrCa中发挥重要的致癌作用，并且GB对某些癌症的治疗具有重要意义。
