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

iScience (2021-11-16)
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
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Phosphotyrosine Antibody, clone 4G10®, agarose conjugate, clone 4G10®, Upstate®, from mouse
Millipore
Protein A Agarose, Protein A Agarose Beads for the purification of human, mouse & rabbit immunoglobins.
Sigma-Aldrich
Anti-Phosphotyrosine Antibody, clone 4G10®, clone 4G10®, Upstate®, from mouse
Millipore
Protein G Agarose, Fast Flow, Protein G Agarose, Fast Flow suitable for medium and low pressure chromatography of IgG from mouse, sheep, and rabbit, and for immunoprecipitations.