GABRP, the π subunit of the gamma-aminobutyric acid (GABA) A receptor, is expressed in many non-neuronal tissues. It is involved in neurotransmitter-initiated signalling pathways, which are implicated in tumour initiation and progression. It can interact with other proteins to regulate important signalling pathways and biological processes [1,3].

In pancreatic cancer, GABRP is highly expressed, associated with poor prognosis, and promotes tumour growth, metastasis, and gemcitabine resistance. It interacts with KCNN4 to induce Ca²⁺ entry, activating NF-κB signalling and facilitating macrophage infiltration [1,2]. In triple-negative breast cancer, GABRP interacts with EGFR, sustaining its expression, cell stemness, and chemotherapy resistance [3]. In oesophageal cancer, overexpression of GABRP inhibits cancer progression by regulating CFTR [4]. In pancreatic cancer, it also promotes metastasis via the MEK/ERK signalling pathway [5]. In bronchial asthma, blocking GABA signalling through Gabrp inhibits mouse Club cell proliferation and differentiation into goblet cells [6].

In conclusion, GABRP plays diverse roles in various biological processes and disease conditions. In cancer, it often acts as an oncogenic factor, promoting tumour development and progression in multiple ways. Its study in different disease models helps to understand the underlying molecular mechanisms and may provide potential therapeutic targets.

References:

1. Jiang, Shu-Heng, Zhu, Li-Li, Zhang, Man, Hou, Shangwei, Zhang, Zhi-Gang. 2019. GABRP regulates chemokine signalling, macrophage recruitment and tumour progression in pancreatic cancer through tuning KCNN4-mediated Ca2+ signalling in a GABA-independent manner. In Gut, 68, 1994-2006. doi:10.1136/gutjnl-2018-317479. https://pubmed.ncbi.nlm.nih.gov/30826748/

2. Chen, Chen, Wu, Binfeng, Wang, Mingge, Huang, Zhaohui, Shi, Jin-Song. 2022. GABRP promotes CD44s-mediated gemcitabine resistance in pancreatic cancer. In PeerJ, 10, e12728. doi:10.7717/peerj.12728. https://pubmed.ncbi.nlm.nih.gov/35846884/

3. Li, Xiyin, Wang, Hairui, Yang, Xing, Nie, Jianyun, Jiao, Baowei. 2021. GABRP sustains the stemness of triple-negative breast cancer cells through EGFR signaling. In Cancer letters, 514, 90-102. doi:10.1016/j.canlet.2021.04.028. https://pubmed.ncbi.nlm.nih.gov/34023418/

4. Zhang, Jingzhi, Liu, Xue, Zeng, Ling, Hu, Ying. 2024. GABRP inhibits the progression of oesophageal cancer by regulating CFTR: Integrating bioinformatics analysis and experimental validation. In International journal of experimental pathology, 105, 118-132. doi:10.1111/iep.12513. https://pubmed.ncbi.nlm.nih.gov/38989629/

5. Meng, Yong, Li, Rui, Geng, Shuaiming, Hao, Ji, Xu, Zhen. 2023. GABRP Promotes the Metastasis of Pancreatic Cancer by Activation of the MEK/ERK Signaling Pathway. In Biochemical genetics, 62, 242-253. doi:10.1007/s10528-023-10410-z. https://pubmed.ncbi.nlm.nih.gov/37326897/

6. Wang, An, Zhang, Qiuyang, Wang, Yongmei, Li, Li, Chen, Huaiyong. 2021. Inhibition of Gabrp reduces the differentiation of airway epithelial progenitor cells into goblet cells. In Experimental and therapeutic medicine, 22, 720. doi:10.3892/etm.2021.10152. https://pubmed.ncbi.nlm.nih.gov/34007329/