Stc2, or stanniocalcin 2, is a glycoprotein. It plays roles in regulating calcium and phosphorus homeostasis, glucose homeostasis, and phosphorus metastasis. It is also involved in processes like neuron cell differentiation, angiogenesis, wound healing, fertility, embryo development, and is significantly associated with cancer. Its expression is regulated transcriptionally and post-transcriptionally, and is stimulated under stress conditions such as ER stress, hypoxia, and nutrient deprivation [1,6].

In cancer research, STC2 has been shown to have multiple effects. In esophageal squamous cell carcinoma, knockdown of STC2 could potentially overcome radioresistance as STC2 activates PRMT5 to induce radioresistance through DNA damage repair and ferroptosis pathways [2]. In hepatocellular carcinoma, STC2 knockdown inhibits cell proliferation and glycolysis via promoting autophagy by the PI3K/Akt/mTOR pathway. Also, STC2 may mediate the difference between Nrf1α-deficient and Nrf2-deficient cells, and could be a potential therapeutic target for HCC [3,4]. In gastric cancer, high expression of the STC2 gene was significantly related to the disease, and it may be used as a biomarker to assist in tumor removal surgery [6]. A pan-cancer analysis indicated STC2 as a potential prognostic biomarker for pan-cancer and a new immunotherapy target [5].

In conclusion, Stc2 is a multifunctional glycoprotein involved in various physiological and pathological processes. Its role in cancer, especially in tumor growth, invasion, metastasis, and response to therapies, has been well-studied. The use of loss-of-function models, though not specifically KO/CKO mouse models in all references, has helped reveal its significance in cancer-related biological processes, providing potential directions for cancer treatment.