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
Affiliations
Bo Wei
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
Yini Zhu
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
Peng Yang
Department of Breast & Endocrine Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, China
Yong Han
Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430022, China
Suyun Wang
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
Xiaomei Wang
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
Shuai Xia
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
Xiaoguang Song
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
Zhongling Zhang
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
Sheng Wang
Key Laboratory of Molecular Biophysics of MOE, College of Life Science and Technology, Huazhong University of Science and Technology (HUST), Wuhan 430074, China
Philippe Rondard
Institut de Génomique Fonctionnelle (IGF), Université de Montpellier, CNRS, INSERM, 34094 Montpellier, France
Jean-Philippe Pin
Institut de Génomique Fonctionnelle (IGF), Université de Montpellier, CNRS, INSERM, 34094 Montpellier, France
Xinnong Jiang
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; Corresponding author
Jianfeng Liu
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; Corresponding author
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.