Stc1, or Stanniocalcin-1, is a gene with diverse functions. It is involved in multiple biological processes, such as cell proliferation, migration, and invasion. In cancer, it is associated with signaling pathways like TGF-β/SMAD4, YAP/CCL2/VEGFA/AKT, and Notch1, influencing tumor progression, metastasis, and stemness [1,3,5]. In asthma, it may act as an epithelium-derived relaxing factor (EpDRF) by modulating calcium channels [4].

In cancer research, various in vitro and in vivo experiments have been conducted. For example, in glioblastoma, silencing Stc1 inhibited cell proliferation and invasion through the TGF-β/SMAD4 pathway [3]. In melanoma, STC1 enhanced metastasis by promoting M2 macrophage recruitment and polarization, and silencing STC1 enhanced the efficacy of PD-1 immunotherapy [1]. In colorectal cancer, A20 upregulated STC1 to block the "eat-me" signal, promoting immune evasion [2]. In hepatocellular carcinoma, CAF-derived STC1 promoted tumor stemness via the Notch1 signaling pathway [5]. In ovarian cancer, STC1 promoted metastasis, lipid metabolism, and cisplatin chemoresistance via the FOXC2/ITGB6 signaling axis [6]. In bladder cancer, high STC1 expression predicted poor prognosis and was related to immune characteristics [7]. In colitis, STC1-deficient mice (Stc1INT-KO) were resistant to DSS-induced colitis, as STC1 mediates oxidative stress-associated parthanatos and aggravates inflammation via the STC1-PARP1-JNK interactions [8].

In conclusion, Stc1 is a multifunctional gene involved in cancer progression, metastasis, immune evasion, and stemness, as well as in asthma airway hyperresponsiveness and colitis. Gene-knockout models, especially Stc1INT-KO mice in colitis, have been crucial in revealing its role in these disease conditions, providing insights into potential therapeutic targets.

References:

1. Ren, Zhaozhou, Xu, Zhijie, Chang, Xiyue, Liu, Jie, Xiao, Wan'an. 2024. STC1 competitively binding βPIX enhances melanoma progression via YAP nuclear translocation and M2 macrophage recruitment through the YAP/CCL2/VEGFA/AKT feedback loop. In Pharmacological research, 204, 107218. doi:10.1016/j.phrs.2024.107218. https://pubmed.ncbi.nlm.nih.gov/38768671/

2. Luo, Min, Wang, Xueping, Wu, Shaocong, Wang, Fang, Fu, Liwu. 2023. A20 promotes colorectal cancer immune evasion by upregulating STC1 expression to block "eat-me" signal. In Signal transduction and targeted therapy, 8, 312. doi:10.1038/s41392-023-01545-x. https://pubmed.ncbi.nlm.nih.gov/37607946/

3. Xiong, Yan, Wang, Qibai. 2019. STC1 regulates glioblastoma migration and invasion via the TGF‑β/SMAD4 signaling pathway. In Molecular medicine reports, 20, 3055-3064. doi:10.3892/mmr.2019.10579. https://pubmed.ncbi.nlm.nih.gov/31432189/

4. Xu, Jiayan, Meng, Yaqi, Jia, Man, Adcock, Ian M, Yao, Xin. 2021. Epithelial expression and role of secreted STC1 on asthma airway hyperresponsiveness through calcium channel modulation. In Allergy, 76, 2475-2487. doi:10.1111/all.14727. https://pubmed.ncbi.nlm.nih.gov/33378582/

5. Bai, Shuya, Zhao, Yuchong, Chen, Wei, Cheng, Bin, Wang, Ronghua. 2023. The stromal-tumor amplifying STC1-Notch1 feedforward signal promotes the stemness of hepatocellular carcinoma. In Journal of translational medicine, 21, 236. doi:10.1186/s12967-023-04085-8. https://pubmed.ncbi.nlm.nih.gov/37004088/

6. Lin, Feikai, Li, Xiaoduan, Wang, Xinjing, Wang, Ziliang, Wang, Xipeng. 2022. Stanniocalcin 1 promotes metastasis, lipid metabolism and cisplatin chemoresistance via the FOXC2/ITGB6 signaling axis in ovarian cancer. In Journal of experimental & clinical cancer research : CR, 41, 129. doi:10.1186/s13046-022-02315-3. https://pubmed.ncbi.nlm.nih.gov/35392966/

7. Sun, Jiale, Wei, Xuedong, You, Jiawei, Ling, Zhixin, Hou, Jianquan. 2021. STC1 is a Novel Biomarker Associated with Immune Characteristics and Prognosis of Bladder Cancer. In International journal of general medicine, 14, 5505-5516. doi:10.2147/IJGM.S329723. https://pubmed.ncbi.nlm.nih.gov/34539184/

8. Zhu, Liguo, Xie, Zhuo, Yang, Guang, Li, Li, Zhang, Shenghong. 2023. Stanniocalcin-1 Promotes PARP1-Dependent Cell Death via JNK Activation in Colitis. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 11, e2304123. doi:10.1002/advs.202304123. https://pubmed.ncbi.nlm.nih.gov/38088577/