SDC1, also known as Syndecan-1 or CD138, is a key cell surface adhesion molecule crucial for maintaining cell morphology and interactions with the surrounding microenvironment. It binds to various ligands and influences cell growth and reproduction via the activation of pathways such as Wnt, FLIP long, VEGFR, MAPK/ERK, and MAPK/JNK [2]. SDC1 is involved in multiple biological processes, and its abnormal expression is associated with various diseases, especially cancers [2-8, 10].

In cancer research, SDC1 shows different effects in various types of cancers. In pancreatic cancer, scRNA-seq analysis found CCL5-SDC1/4 receptor-ligand interactions between T cells and tumor cells, and CCL5 promoted tumor cell migration via interacting with SDC1 in vitro [1]. In breast cancer, SDC1 is highly expressed, and silencing it blocks cell proliferation, migration, and invasion [5]. In contrast, in colorectal cancer, reduced SDC1 expression is related to poor prognosis, while high SDC1 expression in stromal cells is associated with a good prognosis [6,8]. In gallbladder cancer, SDC1 knockdown promotes cell proliferation, invasion, and migration possibly by regulating the ERK/Snail signaling pathway and inducing EMT [7]. In hepatic carcinoma, SDC1 promotes cisplatin resistance via the PI3K-AKT pathway [4]. In glioblastoma, SDC1 overexpression contributes to radioresistance by influencing the fusion of autophagosomes with lysosomes through the SDC1-TGM2-FLOT1-BHMT complex [3].

In conclusion, SDC1 plays diverse and complex roles in different biological processes and diseases, especially in cancer. Its abnormal expression can either promote or inhibit cancer progression depending on the cancer type. Studies on SDC1 help to understand the molecular mechanisms of diseases and may provide new targets for immunotherapy and cancer treatment.

References:

1. Chen, Kai, Wang, Yazhou, Hou, Yuting, Tian, Xiaodong, Yang, Yinmo. 2022. Single cell RNA-seq reveals the CCL5/SDC1 receptor-ligand interaction between T cells and tumor cells in pancreatic cancer. In Cancer letters, 545, 215834. doi:10.1016/j.canlet.2022.215834. https://pubmed.ncbi.nlm.nih.gov/35917973/

2. Liao, Shiyao, Liu, Chang, Zhu, Guiying, Yang, Ying, Wang, Changmiao. 2019. Relationship between SDC1 and cadherin signalling activation in cancer. In Pathology, research and practice, 216, 152756. doi:10.1016/j.prp.2019.152756. https://pubmed.ncbi.nlm.nih.gov/31810587/

3. Zeng, Liang, Zheng, Wang, Liu, Xinglong, Zhang, Jianghong, Shao, Chunlin. 2023. SDC1-TGM2-FLOT1-BHMT complex determines radiosensitivity of glioblastoma by influencing the fusion of autophagosomes with lysosomes. In Theranostics, 13, 3725-3743. doi:10.7150/thno.81999. https://pubmed.ncbi.nlm.nih.gov/37441590/

4. Yu, Liquan, Xu, Hong, Zhang, Song, Chen, Jiangming, Yu, Zhongshan. 2020. SDC1 promotes cisplatin resistance in hepatic carcinoma cells via PI3K-AKT pathway. In Human cell, 33, 721-729. doi:10.1007/s13577-020-00362-6. https://pubmed.ncbi.nlm.nih.gov/32314115/

5. Song, Guoqing, Ma, Yao, Ma, Yinghan, Cao, Yanan, Zhao, Yi. . miR-335-5p Targets SDC1 to Regulate the Progression of Breast Cancer. In Critical reviews in eukaryotic gene expression, 32, 21-31. doi:10.1615/CritRevEukaryotGeneExpr.2022041813. https://pubmed.ncbi.nlm.nih.gov/35997115/

6. Li, Zhejie, He, Shujin, Liu, Jianli, Li, Lei, Wang, Wei. 2022. High expression of SDC1 in stromal cells is associated with good prognosis in colorectal cancer. In Anti-cancer drugs, 34, 479-482. doi:10.1097/CAD.0000000000001441. https://pubmed.ncbi.nlm.nih.gov/36730554/

7. Liu, Zixiang, Jin, Hao, Yang, Song, Wen, Bo, Zhou, Shaobo. . SDC1 knockdown induces epithelial-mesenchymal transition and invasion of gallbladder cancer cells via the ERK/Snail pathway. In The Journal of international medical research, 48, 300060520947883. doi:10.1177/0300060520947883. https://pubmed.ncbi.nlm.nih.gov/32812461/

8. Li, Kaizhi, Li, Lei, Wu, Xiaoxiao, Li, Yan, Wang, Wei. 2019. Loss of SDC1 Expression Is Associated with Poor Prognosis of Colorectal Cancer Patients in Northern China. In Disease markers, 2019, 3768708. doi:10.1155/2019/3768708. https://pubmed.ncbi.nlm.nih.gov/31182980/