Stc2, or stanniocalcin 2, is a glycoprotein. It plays crucial roles in regulating calcium and phosphorus homeostasis, glucose homeostasis, and phosphorus metastasis [5]. It has also been implicated in neuron cell differentiation, angiogenesis, wound healing, fertility, embryo development, and cancer [6]. In cancer, its expression is regulated at transcriptional and post-transcriptional levels, and is significantly stimulated under stress conditions like ER stress, hypoxia, and nutrient deprivation [1].

Stc2 has been widely studied in the context of various cancers. In esophageal squamous cell carcinoma, knockdown of Stc2 may overcome radioresistance as it was found to activate PRMT5 to promote DNA damage repair and ferroptosis-related radioresistance [2]. In hepatocellular carcinoma, Stc2 knockdown inhibits cell proliferation and glycolysis through promoting autophagy by the PI3K/Akt/mTOR pathway [4]. Also, Stc2 is upregulated in Nrf1α-deficient cells but downregulated in Nrf2-deficient cells, and it could be a potential biomarker and therapeutic target [3]. In gastric cancer, high expression of the Stc2 gene was significantly related to the disease, and it may be used to determine tumor borders during surgery [6].

In conclusion, Stc2 is involved in multiple biological processes and is closely associated with cancer development and progression. Studies on Stc2, especially through loss-of-function experiments in cancer cells, have revealed its roles in promoting tumor growth, invasion, metastasis, and radioresistance. This understanding of Stc2 provides potential directions for developing targeted cancer therapies.

References:

1. Qie, Shuo, Sang, Nianli. 2022. Stanniocalcin 2 (STC2): a universal tumour biomarker and a potential therapeutical target. In Journal of experimental & clinical cancer research : CR, 41, 161. doi:10.1186/s13046-022-02370-w. https://pubmed.ncbi.nlm.nih.gov/35501821/

2. Jiang, Kan, Yin, Xin, Zhang, Qingyi, Yu, Hao, Yan, Senxiang. 2023. STC2 activates PRMT5 to induce radioresistance through DNA damage repair and ferroptosis pathways in esophageal squamous cell carcinoma. In Redox biology, 60, 102626. doi:10.1016/j.redox.2023.102626. https://pubmed.ncbi.nlm.nih.gov/36764215/

3. Bu, Qiqi, Deng, Yangxu, Wang, Qing, Pei, Zhigang, Zhang, Yiguo. 2023. STC2 is a potential biomarker of hepatocellular carcinoma with its expression being upregulated in Nrf1α-deficient cells, but downregulated in Nrf2-deficient cells. In International journal of biological macromolecules, 253, 127575. doi:10.1016/j.ijbiomac.2023.127575. https://pubmed.ncbi.nlm.nih.gov/37866563/

4. Li, Ding, Xiong, Yuanyuan, Li, Muzi, Yan, Huifeng, Xiang, Hua. 2024. STC2 knockdown inhibits cell proliferation and glycolysis in hepatocellular carcinoma through promoting autophagy by PI3K/Akt/mTOR pathway. In Archives of biochemistry and biophysics, 761, 110149. doi:10.1016/j.abb.2024.110149. https://pubmed.ncbi.nlm.nih.gov/39271096/

5. Jiang, Zhong-Hui, Shen, Xianfeng, Wei, Yanhong, Xia, Lingyun, Leng, Weidong. 2022. A Pan-Cancer Analysis Reveals the Prognostic and Immunotherapeutic Value of Stanniocalcin-2 (STC2). In Frontiers in genetics, 13, 927046. doi:10.3389/fgene.2022.927046. https://pubmed.ncbi.nlm.nih.gov/35937984/

6. Qiu, Junqi, Chen, Xihan, Zheng, Zengpai. 2023. Evaluating STC2 gene RNA in peripheral blood serum of gastric cancer patients. In Cellular and molecular biology (Noisy-le-Grand, France), 69, 72-75. doi:10.14715/cmb/2023.69.12.12. https://pubmed.ncbi.nlm.nih.gov/38063115/