Gpc5, also known as Glypican-5, is a member of heparan sulfate proteoglycans. It plays a role in various biological processes and is involved in multiple signaling pathways. In cancer, its role is of particular interest, as it has been implicated in influencing cancer progression, and its expression is associated with prognosis in certain cancers [1,2,3,4,5,6,7]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, can be valuable for studying its function.

In lung cancer, Gpc5 functions as a tumor suppressor. Overexpression of Gpc5 transcriptionally enhances CTDSP1 expression via the AhR-ARNT pathway, inhibiting lung cancer cell proliferation. Exosomes from Gpc5-overexpressing lung cancer cells also repress human lymphatic endothelial cells, affecting tube formation and migration [1]. Additionally, Gpc5 polymorphism rs2352028 C > T is associated with a better prognosis in Chinese lung cancer patients [2]. In gastric cancer, the lncRNA Gpc5-AS1 stabilizes Gpc5 mRNA, reducing tumor progression [3]. In lung adenocarcinoma, Gpc5 is epigenetically silenced, and its overexpression inhibits cell proliferation, migration, invasion, and tumor growth by suppressing the Wnt/β-catenin signaling pathway [5]. In prostate cancer, the low expression of Gpc5 is associated with increased serum prostate-specific antigen, higher Gleason scores, advanced tumor stage, positive lymph node metastasis, and biochemical recurrence, and is an independent prognostic factor for overall survival [7].

In conclusion, Gpc5 is an important gene, and its role as a tumor suppressor is evident in multiple cancer types, including lung and prostate cancer. Model-based research, such as through KO or CKO mouse models, would likely further elucidate its function in these disease conditions, potentially providing new insights for cancer treatment strategies.

References:

1. Yang, Xin, Chen, Yan, Zhou, You, Jiang, Jing Ting, Ji, Mei. 2021. GPC5 suppresses lung cancer progression and metastasis via intracellular CTDSP1/AhR/ARNT signaling axis and extracellular exosome secretion. In Oncogene, 40, 4307-4323. doi:10.1038/s41388-021-01837-y. https://pubmed.ncbi.nlm.nih.gov/34079082/

2. Wang, Fan, Li, Yutao, Li, Zhengxing, Shen, Bo, Wu, Junjie. 2022. Prognostic value of GPC5 polymorphism rs2352028 and clinical characteristics in Chinese lung cancer patients. In Future oncology (London, England), 18, 3165-3177. doi:10.2217/fon-2022-0319. https://pubmed.ncbi.nlm.nih.gov/36165234/

3. Bo, Guo, Liu, Yijie, Li, Wen, Wang, Wenjing, Huang, Chen. 2022. The novel lncRNA GPC5-AS1 stabilizes GPC5 mRNA by competitively binding with miR-93/106a to suppress gastric cancer cell proliferation. In Aging, 14, 1767-1781. doi:10.18632/aging.203901. https://pubmed.ncbi.nlm.nih.gov/35183057/

4. Zhao, Zhengyuan, Han, Chengguang, Liu, Juntao, Wang, Yi, Cheng, Liya. 2014. GPC5, a tumor suppressor, is regulated by miR-620 in lung adenocarcinoma. In Molecular medicine reports, 9, 2540-6. doi:10.3892/mmr.2014.2092. https://pubmed.ncbi.nlm.nih.gov/24682381/

5. Yuan, S, Yu, Z, Liu, Q, Bai, L, Li, Y. 2016. GPC5, a novel epigenetically silenced tumor suppressor, inhibits tumor growth by suppressing Wnt/β-catenin signaling in lung adenocarcinoma. In Oncogene, 35, 6120-6131. doi:10.1038/onc.2016.149. https://pubmed.ncbi.nlm.nih.gov/27157618/

6. Song, Qiang, Yan, Hong-Zhu, Wang, Rong, Zuo, Qing-Jun, Song, Xu. . [Correlation of the expressions of 4-HNE and GPC5 with the progression of prostate cancer]. In Zhonghua nan ke xue = National journal of andrology, 29, 19-24. doi:. https://pubmed.ncbi.nlm.nih.gov/37846827/

7. Zhang, Changwen, Liu, Zhifei, Wang, Li, Xu, Yong, Zhang, Zhihong. 2015. Prognostic significance of GPC5 expression in patients with prostate cancer. In Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 37, 6413-8. doi:10.1007/s13277-015-4499-3. https://pubmed.ncbi.nlm.nih.gov/26631038/