Gtpbp4, also known as Guanosine triphosphate binding protein 4, is a key regulator involved in cell cycle progression and MAPK activation [1]. It is associated with multiple cellular processes such as GTP binding and rRNA processing, and is part of pathways related to aerobic glycolysis, epithelial-mesenchymal transition (EMT), and STAT3 signaling [1]. Gtpbp4 has been found to be closely related to genes like NIFK, WDR12, and RPF2 [2].

In various cancers, functional studies including loss-of-function experiments have revealed its oncogenic role. In hepatocellular carcinoma (HCC), knockdown of Gtpbp4 in cell lines and in vivo xenograft nude mice models showed inhibition of cell proliferation, colony formation, and tumorigenesis, with cell cycle arrest in G2/M and promotion of apoptosis [7]. Gtpbp4 promotes HCC growth and metastasis by inducing dimeric pyruvate kinase M2 (PKM2) formation through protein sumoylation modification to enhance aerobic glycolysis [1]. In non-small cell lung cancer, knocking down Gtpbp4 in A549 and Calu-1 lung adenocarcinoma cells inhibited cell proliferation and invasion, and in a mouse lung cancer model, the lung weight and number of lung surface nodules decreased significantly in the LLC-Gtpbp4 KO group [3]. In gastric cancer, stable knockdown of Gtpbp4 inhibited cell proliferation and promoted apoptosis, with activation of p53 and its related signaling [4]. In colorectal carcinoma, knockdown of Gtpbp4 impeded cell motility and tumor metastasis, while its overexpression enhanced these processes [5]. In breast cancer, knockdown of Gtpbp4 in cell lines reduced cell activity, migration, and proliferation [6]. In lung adenocarcinoma, Gtpbp4 knockdown in cells inhibited proliferation and metastasis, promoted apoptosis, and enhanced sensitivity to TP [8].

In conclusion, Gtpbp4 plays a crucial role in promoting the progression of multiple cancers, including HCC, non-small cell lung cancer, gastric cancer, colorectal carcinoma, breast cancer, and lung adenocarcinoma. Gene knockout and knockdown models in these cancers have been instrumental in uncovering its role in promoting cell proliferation, metastasis, and inhibiting apoptosis, highlighting its potential as a therapeutic target.

References:

1. Zhou, Qiang, Yin, Yirui, Yu, Mincheng, Zhou, Chenhao, Ren, Ning. 2022. GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism. In Redox biology, 56, 102458. doi:10.1016/j.redox.2022.102458. https://pubmed.ncbi.nlm.nih.gov/36116159/

2. Chen, Jia, Zhang, Jie, Zhang, Zhiwei. 2021. Upregulation of GTPBP4 Promotes the Proliferation of Liver Cancer Cells. In Journal of oncology, 2021, 1049104. doi:10.1155/2021/1049104. https://pubmed.ncbi.nlm.nih.gov/34712323/

3. Wu, Junlu, Chen, Guofei, Wang, Weiwei, Quan, Wenqiang, Wang, Lixin. 2022. GTPBP4: A New Therapeutic Target Gene Promotes Tumor Progression in Non-Small Cell Lung Cancer via EMT. In Journal of oncology, 2022, 2164897. doi:10.1155/2022/2164897. https://pubmed.ncbi.nlm.nih.gov/36405249/

4. Li, Li, Pang, Xunlei, Zhu, Zuan, Cao, Jiang, Fei, Sujuan. 2018. GTPBP4 Promotes Gastric Cancer Progression via Regulating P53 Activity. In Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 45, 667-676. doi:10.1159/000487160. https://pubmed.ncbi.nlm.nih.gov/29408813/

5. Yu, Haitao, Jin, Sufeng, Zhang, Na, Xu, Qi. 2016. Up-regulation of GTPBP4 in colorectal carcinoma is responsible for tumor metastasis. In Biochemical and biophysical research communications, 480, 48-54. doi:10.1016/j.bbrc.2016.10.010. https://pubmed.ncbi.nlm.nih.gov/27720713/

6. Hu, Yiming, Xie, Jiaheng, Chen, Liang, Yin, Lu, Ji, Jing. 2022. Integrated Analysis of Genomic and Transcriptomic Profiles Identified the Role of GTP Binding Protein-4 (GTPBP4) in Breast Cancer. In Frontiers in pharmacology, 13, 880445. doi:10.3389/fphar.2022.880445. https://pubmed.ncbi.nlm.nih.gov/35784753/

7. Liu, Wen-Bin, Jia, Wei-Dong, Ma, Jin-Liang, Peng, Yan, Wang, Wei. 2017. Knockdown of GTPBP4 inhibits cell growth and survival in human hepatocellular carcinoma and its prognostic significance. In Oncotarget, 8, 93984-93997. doi:10.18632/oncotarget.21500. https://pubmed.ncbi.nlm.nih.gov/29212203/

8. Zhang, Zhiqian, Wang, Juan, Mao, Jiayan, Chen, Wei, Wang, Wei. 2020. Determining the Clinical Value and Critical Pathway of GTPBP4 in Lung Adenocarcinoma Using a Bioinformatics Strategy: A Study Based on Datasets from The Cancer Genome Atlas. In BioMed research international, 2020, 5171242. doi:10.1155/2020/5171242. https://pubmed.ncbi.nlm.nih.gov/33134380/