SDC2, also known as Syndecan-2, is a gene with diverse functions. It is involved in multiple signaling pathways. In the context of cancer, it has been linked to the activation of the AKT signaling pathway, for example, through interaction with the PDK1-PH domain, facilitating PDK1 membrane translocation to promote AKT activation. It can also act as a co-receptor for FGF2 and is involved in the FGF2-AKT signaling axis [1].

In gastric cancer, SDC2 is highly expressed, and its up-regulation is correlated with poor prognosis. Depletion of SDC2 significantly suppresses the growth and invasive capability of gastric cancer cells, while overexpressing SDC2 has the opposite effect [1]. In colorectal cancer, studies on the methylation of SDC2 in stool samples show its potential as a biomarker. For instance, the methylation level of fecal SDC2 in colorectal cancer patients is different from that in healthy individuals, and the detection of SDC2 methylation has a relatively high sensitivity and specificity for colorectal cancer diagnosis. Combining SDC2 with other genes like NDRG4, TFPI2 can improve the diagnostic performance [2,3,5,6]. Also, in human spermatogonial stem cells, SDC2 is activated by PTN from Leydig cells and is involved in modulating cell proliferation and survival [4].

In conclusion, SDC2 plays crucial roles in multiple biological processes, especially in cancer progression and spermatogonial stem cell regulation. Studies on SDC2 gene-knockout or related functional models have provided insights into its functions in gastric and colorectal cancer, and male infertility, highlighting its potential as a diagnostic marker and therapeutic target in these disease areas.

References:

1. You, Li, Dou, Yi, Zhang, Yu, Wei, Gong-Hong, Xu, Dazhi. 2023. SDC2 Stabilization by USP14 Promotes Gastric Cancer Progression through Co-option of PDK1. In International journal of biological sciences, 19, 3483-3498. doi:10.7150/ijbs.84331. https://pubmed.ncbi.nlm.nih.gov/37496999/

2. Li, Nanyang, Li, Chunmei, Zhang, Xuejun, Liang, Jingjing, Wang, Fengqiang. 2023. Diagnostic value of human fecal SDC2 gene in colorectal cancer. In American journal of translational research, 15, 2843-2849. doi:. https://pubmed.ncbi.nlm.nih.gov/37193183/

3. Long, Lu, Sun, Qian, Yang, Fang, He, Qing, Yi, Bin. 2024. Significance of SDC2 and NDRG4 methylation in stool for colorectal cancer diagnosis. In Clinical biochemistry, 124, 110717. doi:10.1016/j.clinbiochem.2024.110717. https://pubmed.ncbi.nlm.nih.gov/38224931/

4. Zhao, Xueheng, Liu, Lvjun, Huang, Zenghui, Zhang, Huan, Zhou, Dai. 2024. PTN from Leydig cells activates SDC2 and modulates human spermatogonial stem cell proliferation and survival via GFRA1. In Biological research, 57, 66. doi:10.1186/s40659-024-00546-6. https://pubmed.ncbi.nlm.nih.gov/39285301/

5. Zhang, Weisong, Yang, Chaogang, Wang, Shuyi, Zheng, Jinsen, Xiong, Bin. 2021. SDC2 and TFPI2 Methylation in Stool Samples as an Integrated Biomarker for Early Detection of Colorectal Cancer. In Cancer management and research, 13, 3601-3617. doi:10.2147/CMAR.S300861. https://pubmed.ncbi.nlm.nih.gov/33958894/

6. Zhang, Lianglu, Dong, Lanlan, Lu, Changming, Lin, Jun, Yin, Lei. 2021. Methylation of SDC2/TFPI2 and Its Diagnostic Value in Colorectal Tumorous Lesions. In Frontiers in molecular biosciences, 8, 706754. doi:10.3389/fmolb.2021.706754. https://pubmed.ncbi.nlm.nih.gov/35004840/