PYGB, also known as brain-type glycogen phosphorylase (GP), is the rate-limiting enzyme of glycogen catabolism [2]. It plays a crucial role in glycogen metabolism, a form of essential metabolic reprogramming in cells. By breaking down glycogen, PYGB releases glucose-6-phosphate (G6P), which can then enter glycolysis or other metabolic pathways, thus influencing energy metabolism in cells.

In various diseases, PYGB has been found to be significantly involved. In cholangiocarcinoma (CCA), PYGB is upregulated in tissues and promotes carcinogenesis and cell proliferation. Hypoxia stimulates its activity in a phosphoglycerate kinase 1-dependent manner, facilitating aerobic glycolysis [1]. In non-small cell lung cancer (NSCLC), PYGB expression is positively related to TNM stage and lymph node metastasis. Overexpression promotes cell proliferation, migration, and invasion by activating the Wnt-β-catenin signaling pathway [3]. Similar findings are seen in gastric cancer, where PYGB depletion suppresses tumor growth and metastasis via the Wnt/β-catenin pathway [5]. In esophageal squamous carcinoma, androgen receptor-targeted PYGB contributes to tumor progression and metabolic reprogramming [4]. In pancreatic cancer, high expression of PYGB promotes cell proliferation, invasion, and metastasis, and it may be a novel diagnostic biomarker and gene therapy target [7]. In osteosarcoma cell lines, knockdown of PYGB inhibits cell proliferation, invasion, and migration [6].

In conclusion, PYGB is essential for glycogen metabolism and energy supply in cells. Through gene-knockdown or KO-like experiments in cell lines and animal models, it has been shown to play a promoting role in the progression of multiple cancers, including CCA, NSCLC, gastric cancer, esophageal squamous carcinoma, pancreatic cancer, and osteosarcoma. Understanding the function of PYGB in these disease conditions provides potential therapeutic targets for treating these cancers.

References:

1. Pan, Yani, Zhou, Yue, Shen, Yonghua, Wang, Zhangding, Wang, Lei. . Hypoxia Stimulates PYGB Enzymatic Activity to Promote Glycogen Metabolism and Cholangiocarcinoma Progression. In Cancer research, 84, 3803-3817. doi:10.1158/0008-5472.CAN-24-0088. https://pubmed.ncbi.nlm.nih.gov/39163511/

2. Yang, Caiting, Wang, Haojun, Shao, Miaomiao, Cai, Qianqian, Wu, Changxin. 2024. Brain-Type Glycogen Phosphorylase (PYGB) in the Pathologies of Diseases: A Systematic Review. In Cells, 13, . doi:10.3390/cells13030289. https://pubmed.ncbi.nlm.nih.gov/38334681/

3. Xiao, Lina, Wang, Wei, Huangfu, Qiuqiang, Tao, Hongjie, Zhang, Jingyi. 2020. PYGB facilitates cell proliferation and invasiveness in non-small cell lung cancer by activating the Wnt-β-catenin signaling pathway. In Biochemistry and cell biology = Biochimie et biologie cellulaire, 98, 565-574. doi:10.1139/bcb-2019-0445. https://pubmed.ncbi.nlm.nih.gov/32191839/

4. Miao, Huikai, Xu, Chunmei, Gao, Wuyou, Ren, Qiannan, Chen, Youfang. 2024. PYGB targeted by androgen receptor contributes to tumor progression and metabolic reprogramming in esophageal squamous carcinoma. In Cellular signalling, 124, 111481. doi:10.1016/j.cellsig.2024.111481. https://pubmed.ncbi.nlm.nih.gov/39442902/

5. Xia, Boning, Zhang, Ke, Liu, Chang. . PYGB Promoted Tumor Progression by Regulating Wnt/β-Catenin Pathway in Gastric Cancer. In Technology in cancer research & treatment, 19, 1533033820926592. doi:10.1177/1533033820926592. https://pubmed.ncbi.nlm.nih.gov/32462986/

6. Zhang, Shuwei, Zhou, Yichi, Zha, Yuanyu, Li, Jingfeng, Jin, Wei. 2018. PYGB siRNA inhibits the cell proliferation of human osteosarcoma cell lines. In Molecular medicine reports, 18, 715-722. doi:10.3892/mmr.2018.9022. https://pubmed.ncbi.nlm.nih.gov/29845265/

7. Ren, Li-Kun, Lu, Ri-Shang, Fei, Xiao-Bin, Wang, Xing, Pan, Yao-Zhen. 2024. Unveiling the role of PYGB in pancreatic cancer: a novel diagnostic biomarker and gene therapy target. In Journal of cancer research and clinical oncology, 150, 127. doi:10.1007/s00432-024-05644-2. https://pubmed.ncbi.nlm.nih.gov/38483604/