Sdcbp, also known as syndecan binding protein or syntenin1, is an adapter protein containing two tandem PDZ domains. It is essential for cellular processes such as cell adhesion, migration, and signal transduction [3,4,6]. Sdcbp has been implicated in multiple signaling pathways including those related to inflammation, apoptosis, angiogenesis, and cancer-related pathways like EGFR-PI3K-Akt and PI3K/AKT/mTOR [2,6,7]. Genetic models, like mouse models, are valuable for studying Sdcbp's functions.

In preclinical KPC mouse cohorts, zinc pyrithione (ZnPT) suppressed pancreatic ductal adenocarcinoma (PDAC) tumour progression by suppressing Sdcbp. Sdcbp was found to promote PDAC proliferation and metastasis by preventing YAP1 from β-TrCP-mediated proteasomal degradation [1]. In a mouse xenograft model and liver metastasis model of colorectal cancer, inhibiting Sdcbp by shRNA transfection or ZnPT treatment hindered proliferation and metastasis while enhancing the efficacy of anti-PD1 treatment. ZnPT treatment also altered the tumour microenvironment of CRC, reducing M2 macrophages and increasing M1 macrophages [4]. In head and neck squamous cell carcinoma (HNSCC) mouse models, Sdcbp-depleted cells formed tumours with decreased mitosis, Ki-67 positivity, and metastasis. Sdcbp expression was associated with Src activation, poor tumour grade, advanced stage, and shorter survival rates in HNSCC patients [5].

In conclusion, Sdcbp plays crucial roles in cell adhesion, migration, and signal transduction. Studies using KO/CKO mouse models have revealed its significant contributions to cancer-related processes, including proliferation, metastasis, and immunotherapy resistance in pancreatic, colorectal, and head and neck cancers. These findings provide potential therapeutic targets for these diseases.

References:

1. Liu, Jing, Bai, Weiwei, Zhou, Tianxing, Yang, Shengyu, Hao, Jihui. 2023. SDCBP promotes pancreatic cancer progression by preventing YAP1 from β-TrCP-mediated proteasomal degradation. In Gut, 72, 1722-1737. doi:10.1136/gutjnl-2022-327492. https://pubmed.ncbi.nlm.nih.gov/36828627/

2. Chen, Qixin, Su, Lina, Liu, Chuanfen, Yin, Qijin, Li, Sufang. 2022. PRKAR1A and SDCBP Serve as Potential Predictors of Heart Failure Following Acute Myocardial Infarction. In Frontiers in immunology, 13, 878876. doi:10.3389/fimmu.2022.878876. https://pubmed.ncbi.nlm.nih.gov/35592331/

3. Pradhan, Anjan K, Maji, Santanu, Das, Swadesh K, Sarkar, Devanand, Fisher, Paul B. . MDA-9/Syntenin/SDCBP: new insights into a unique multifunctional scaffold protein. In Cancer metastasis reviews, 39, 769-781. doi:10.1007/s10555-020-09886-7. https://pubmed.ncbi.nlm.nih.gov/32410111/

4. Yu, Jiahua, Yu, Shijun, Bai, Jin, Gao, Yong, Li, Yandong. 2024. SDCBP modulates tumor microenvironment, tumor progression and anti-PD1 efficacy in colorectal cancer. In Cancer gene therapy, 31, 755-765. doi:10.1038/s41417-024-00758-8. https://pubmed.ncbi.nlm.nih.gov/38555398/

5. Mir, Cristina, Garcia-Mayea, Yoelsis, Garcia, Laia, Carracedo, Ángel, LLeonart, Matilde Esther. 2021. SDCBP Modulates Stemness and Chemoresistance in Head and Neck Squamous Cell Carcinoma through Src Activation. In Cancers, 13, . doi:10.3390/cancers13194952. https://pubmed.ncbi.nlm.nih.gov/34638436/

6. Du, Ruijuan, Huang, Chuntian, Chen, Hanyong, Dong, Zigang, Li, Xiang. 2020. SDCBP/MDA-9/syntenin phosphorylation by AURKA promotes esophageal squamous cell carcinoma progression through the EGFR-PI3K-Akt signaling pathway. In Oncogene, 39, 5405-5419. doi:10.1038/s41388-020-1369-2. https://pubmed.ncbi.nlm.nih.gov/32572158/

7. Qian, Bo, Yao, Zhiheng, Yang, Yang, Li, Na, Wang, Qiao. 2021. Downregulation of SDCBP inhibits cell proliferation and induces apoptosis by regulating PI3K/AKT/mTOR pathway in gastric carcinoma. In Biotechnology and applied biochemistry, 69, 240-247. doi:10.1002/bab.2103. https://pubmed.ncbi.nlm.nih.gov/33432665/