GABAB1e promotes the malignancy of human cancer cells by targeting the tyrosine phosphatase PTPN12

iScience

Yong Han¹  Peng Yang²  Suyun Wang³  Jean-Philippe Pin⁴  Xinnong Jiang⁴  Philippe Rondard⁵  Sheng Wang⁶  Bo Wei⁶  Zhongling Zhang⁶  Yini Zhu⁶  Xiaoguang Song⁶  Shuai Xia⁶  Jianfeng Liu⁶  Xiaomei Wang⁶ 

[1] Endocrine Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, China;;Department of Breast &Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, China;Institut de Génomique Fonctionnelle (IGF), Université de Montpellier, CNRS, INSERM, 34094 Montpellier, France;Key Laboratory of Molecular Biophysics of MOE, College of Life Science and Technology, Huazhong University of Science and Technology (HUST), Wuhan 430074, China;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;

关键词: Biological sciences;    Molecular biology;    Neuroscience;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Neurotransmitter receptors are involved in cancer progression. Among them, the heterodimeric GABAB receptor, activated by the main inhibitory neurotransmitter GABA, is composed of the transmembrane GABAB1 and GABAB2 subunits. The oncogenic role of the isoform GABAB1e (GB1e) containing only the extracellular domain of GABAB1 remains unclear. We revealed that GB1e is largely expressed in human breast cancer (BrCa) cell lines as well as in BrCa tissues where it is upregulated. Moreover, GB1e promoted the malignancy of BrCa cells both in vitro and in vivo. We propose that GB1e favors EGFR signaling by interacting with PTPN12 to disrupt the interaction between EGFR and PTPN12, and phosphorylation of Y230 and Y404 on GB1e is required in this process. Our data highlight that the GABBR1 gene through the expression of the GB1e isoform might play an important oncogenic role in BrCa and that GB1e is of interest for the treatment of some cancers.

【 授权许可】

Unknown