S100A10, also known as p11, is a multifunctional protein belonging to the S100 family of Ca2+-binding proteins, though it itself does not bind Ca2+ [8]. It commonly forms a heterotetramer with Annexin A2, crucial for generating cellular plasmin from plasminogen, which is involved in processes like fibrinolysis, angiogenesis, and wound healing. This complex also plays a role in cancer-related processes such as tumor development, progression, and metastasis [2,3,4,5,6,7].

In HCC, S100A10 promotes cancer initiation, self-renewal, chemoresistance, and metastasis both in vitro and in vivo. It is secreted by HCC cells into extracellular vesicles (EVs), and EV-S100A10 enhances the stemness and metastatic ability of HCC cells, upregulates EGFR, AKT, and ERK signalling, and promotes epithelial-mesenchymal transition. Blockage of EV-S100A10 with a neutralising antibody significantly abrogates these enhancing effects, suggesting it could be a potential therapeutic target and biomarker [1]. In a mouse model, S100A10-deficient mice showed reduced cancer metastasis in the lung. Activation of S100A10 within lung fibroblasts via tumor-derived exosomes increased the expression of CXCL1 and CXCL8 chemokines, accompanied by myeloid-derived suppressor cells (MDSCs) recruitment. Inhibitors of S100A10 can inhibit lung metastasis in vivo [9].

In summary, S100A10 is mainly known for its role in plasminogen activation and its implications in cancer progression. The gene knockout and in vivo studies in mouse models have revealed its significance in promoting cancer metastasis in the context of HCC and lung metastasis, highlighting its potential as a therapeutic target in cancer treatment [1,9].

References:

1. Wang, Xia, Huang, Hongyang, Sze, Karen Man-Fong, Guan, Xinyuan, Ng, Irene Oi-Lin. 2023. S100A10 promotes HCC development and progression via transfer in extracellular vesicles and regulating their protein cargos. In Gut, 72, 1370-1384. doi:10.1136/gutjnl-2022-327998. https://pubmed.ncbi.nlm.nih.gov/36631249/

2. Bharadwaj, Alamelu G, Kempster, Emma, Waisman, David M. 2021. The ANXA2/S100A10 Complex-Regulation of the Oncogenic Plasminogen Receptor. In Biomolecules, 11, . doi:10.3390/biom11121772. https://pubmed.ncbi.nlm.nih.gov/34944416/

3. Bharadwaj, Alamelu, Kempster, Emma, Waisman, David Morton. 2021. The Annexin A2/S100A10 Complex: The Mutualistic Symbiosis of Two Distinct Proteins. In Biomolecules, 11, . doi:10.3390/biom11121849. https://pubmed.ncbi.nlm.nih.gov/34944495/

4. Tantyo, Normastuti Adhini, Karyadi, Azrina Saraswati, Rasman, Siti Zulimas, Devina, Astrella, Sumarpo, Anton. 2018. The prognostic value of S100A10 expression in cancer. In Oncology letters, 17, 1417-1424. doi:10.3892/ol.2018.9751. https://pubmed.ncbi.nlm.nih.gov/30675195/

5. Saiki, Yuriko, Horii, Akira. 2019. Multiple functions of S100A10, an important cancer promoter. In Pathology international, 69, 629-636. doi:10.1111/pin.12861. https://pubmed.ncbi.nlm.nih.gov/31612598/

6. Noye, Tannith M, Lokman, Noor A, Oehler, Martin K, Ricciardelli, Carmela. 2018. S100A10 and Cancer Hallmarks: Structure, Functions, and its Emerging Role in Ovarian Cancer. In International journal of molecular sciences, 19, . doi:10.3390/ijms19124122. https://pubmed.ncbi.nlm.nih.gov/30572596/

7. Kwon, Mijung, MacLeod, Travis J, Zhang, Yi, Waisman, David Morton. 2005. S100A10, annexin A2, and annexin a2 heterotetramer as candidate plasminogen receptors. In Frontiers in bioscience : a journal and virtual library, 10, 300-25. doi:. https://pubmed.ncbi.nlm.nih.gov/15574370/

8. Okura, Gillian C, Bharadwaj, Alamelu G, Waisman, David M. 2023. Recent Advances in Molecular and Cellular Functions of S100A10. In Biomolecules, 13, . doi:10.3390/biom13101450. https://pubmed.ncbi.nlm.nih.gov/37892132/

9. Li, Juan, Zhou, Can, Gao, Xiaoqian, Liu, Jie, Liu, Peijun. 2024. S100A10 promotes cancer metastasis via recruitment of MDSCs within the lungs. In Oncoimmunology, 13, 2381803. doi:10.1080/2162402X.2024.2381803. https://pubmed.ncbi.nlm.nih.gov/39071160/