Scara5, short for scavenger receptor class A member 5, is a gene with significant implications in various biological processes and diseases. It has been associated with pathways related to cancer progression, thrombosis, and hemostasis [1,3]. In the context of cancer, it is considered a potential tumor suppressor in many cancer types, highlighting its importance in tumorigenesis [1,4,5,6,7,8,9,10]. Genetic models such as gene knockout (KO) mouse models could potentially offer insights into its functions [no KO model in references].

In gastric cancer, Scara5 expression is downregulated due to promoter methylation. Overexpression of Scara5 suppresses tumor growth, migration, and invasion by inhibiting epithelial-mesenchymal transition (EMT) and inactivating MMP-2 and MMP-9 [1]. In contrast, in prostate cancer, high Scara5 expression is associated with advanced tumor stage, positive nodal status, and high Gleason-score, suggesting it may serve as a biomarker [2]. In colorectal cancer, bone marrow stromal cell-derived exosomes containing Scara5 inhibit cancer progression by inactivating the PI3K/Akt pathway [4]. In bladder cancer, Scara5, as a downstream factor of the PCAT29/miR-141 axis, inhibits cell proliferation, migration, and invasion [5]. In esophageal squamous cell carcinoma (ESCC), Scara5 suppresses cell cycle, metastasis, and invasion by inducing ferroptosis through combining with ferritin light chain [6]. In oral squamous cell carcinoma (OSCC), Scara5 inhibits cell proliferation, induces apoptosis, and represses EMT by inactivating the STAT3 and PI3K/AKT signaling pathways [7]. In nasopharyngeal carcinoma, Scara5 is downregulated by promoter methylation, and its overexpression inhibits cell migration, invasion, and proliferation, while enhancing sensitivity to chemotherapy [8]. Comprehensive analysis in colorectal cancer shows that Scara5 mRNA levels are downregulated, and low expression is associated with poor prognosis [9]. In melanoma, decreased Scara5 expression is correlated with TNM stage, recurrence, and poor prognosis, and it is related to immune infiltration levels [10]. Also, in thrombosis and hemostasis, genetic variants in Scara5 are associated with plasma levels of von Willebrand factor (VWF) and factor VIII (FVIII), and the receptor may contribute to the clearance of the VWF-FVIII complex [3].

In conclusion, Scara5 plays diverse roles in different biological processes, especially in cancer development and progression, as well as in thrombosis and hemostasis. Studies on Scara5, including those potentially using KO or CKO mouse models in the future, can help further understand its functions and provide potential diagnostic and therapeutic targets for related diseases.

References:

1. Zhang, Hangyu, Liu, Changgang, Wang, Xinbo, Wang, Yongfang, Zheng, Jie. 2021. SCARA5 inhibits gastric cancer progression via epithelial-mesenchymal transition suppression. In Journal of Cancer, 12, 2412-2421. doi:10.7150/jca.52426. https://pubmed.ncbi.nlm.nih.gov/33758617/

2. Flockerzi, Fidelis Andrea, Hohneck, Johannes, Saar, Matthias, Bohle, Rainer Maria, Stahl, Phillip Rolf. 2023. SCARA5 Is Overexpressed in Prostate Cancer and Linked to Poor Prognosis. In Diagnostics (Basel, Switzerland), 13, . doi:10.3390/diagnostics13132211. https://pubmed.ncbi.nlm.nih.gov/37443605/

3. Swystun, Laura L, Michels, Alison, Lillicrap, David. 2023. The contribution of the sinusoidal endothelial cell receptors CLEC4M, stabilin-2, and SCARA5 to VWF-FVIII clearance in thrombosis and hemostasis. In Journal of thrombosis and haemostasis : JTH, 21, 2007-2019. doi:10.1016/j.jtha.2023.04.014. https://pubmed.ncbi.nlm.nih.gov/37085036/

4. Fang, Yu, Wu, Feng, Shang, Guoyin, Yin, Changqing. 2023. SCARA5 in bone marrow stromal cell-derived exosomes inhibits colorectal cancer progression by inactivating the PI3K/Akt pathway. In Genomics, 115, 110636. doi:10.1016/j.ygeno.2023.110636. https://pubmed.ncbi.nlm.nih.gov/37150230/

5. Lu, Xin-Sheng, Huang, Meng-Long, Chen, Li-Bo, Huang, Zhong-Xin, Liu, Shi-Min. 2023. SCARA5 as a downstream factor of PCAT29, inhibits proliferation, migration, and invasion of bladder cancer. In Genomics, 115, 110667. doi:10.1016/j.ygeno.2023.110667. https://pubmed.ncbi.nlm.nih.gov/37315873/

6. Liu, Yanqun, Xiong, Rong, Xiao, Ting, Song, Guiqin, Liu, Kang. 2022. SCARA5 induced ferroptosis to effect ESCC proliferation and metastasis by combining with Ferritin light chain. In BMC cancer, 22, 1304. doi:10.1186/s12885-022-10414-9. https://pubmed.ncbi.nlm.nih.gov/36513999/

7. Huang, Juan, Lv, Chunhua, Zhao, Baoyu, Ji, Zhongqian, Gao, Zhenran. 2023. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways. In Open medicine (Warsaw, Poland), 18, 20230627. doi:10.1515/med-2023-0627. https://pubmed.ncbi.nlm.nih.gov/36785765/

8. Jiang, Xianyao, Jiang, Yu, An, Deqiang, Ji, Ping, Yang, Yucheng. 2023. Methylated tumor suppressor gene SCARA5 inhibits the proliferation, migration and invasion of nasopharyngeal carcinoma. In Epigenomics, 15, 635-650. doi:10.2217/epi-2023-0154. https://pubmed.ncbi.nlm.nih.gov/37554122/

9. Liu, J, Zeng, M L, Shi, P C, Zhang, J L, Xie, Y P. . SCARA5 is a Novel Biomarker in Colorectal Cancer by Comprehensive Analysis. In Clinical laboratory, 66, . doi:10.7754/Clin.Lab.2019.191015. https://pubmed.ncbi.nlm.nih.gov/32658413/

10. Ni, Qinggan, Li, Xia, Huang, Hua, Ge, Zili. 2023. Decreased expression of SCARA5 predicts a poor prognosis in melanoma using bioinformatics analysis. In Frontiers in oncology, 13, 1015358. doi:10.3389/fonc.2023.1015358. https://pubmed.ncbi.nlm.nih.gov/37035142/