Gpc5, a member of heparan sulfate proteoglycans, is involved in multiple biological processes. In cancer, it appears to act as a tumor suppressor in various cancer types. It can interact with different signaling pathways such as the intracellular CTDSP1/AhR/ARNT signaling axis in lung cancer [1]. It may also be related to the Hedgehog pathway in oral squamous cell carcinoma [5].

In lung cancer, Gpc5 has been shown to transcriptionally enhance CTDSP1 expression via the AhR-ARNT pathway, inhibiting lung cancer cell proliferation [1]. Gpc5-overexpressing human lung cancer cells' exosomes can repress human lymphatic endothelial cells, with miR-26b in these exosomes playing a key role [1]. The Gpc5 polymorphism rs2352028 C > T is associated with better prognosis in Chinese lung cancer patients [2].

In gastric cancer, the lncRNA GPC5-AS1 stabilizes Gpc5 mRNA by competitively binding with miR-93/106a, suppressing gastric cancer cell proliferation [3].

In lung adenocarcinoma, Gpc5 is downregulated due to miR-620 upregulation, and its overexpression inhibits proliferation, migration, and invasion of lung cancer cells by suppressing the Wnt/β-catenin signaling pathway [4,6].

In prostate cancer, low Gpc5 expression 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 [7,8].

In conclusion, Gpc5 functions as a tumor suppressor in multiple cancer types including lung, gastric, and prostate cancer. Studies on Gpc5 have provided insights into its role in cancer development and progression through its involvement in various signaling pathways. Understanding Gpc5 may offer potential for new diagnostic and prognostic markers as well as therapeutic targets in these cancer types.