Scara5, known as scavenger receptor class A member 5, has been implicated in multiple biological functions related to disease processes. Although its exact physiological functions in normal biological pathways are not fully elaborated in the provided abstracts, it is often associated with tumor-related pathways and thrombosis-hemostasis-related processes [2].

In cancer research, studies have shown that Scara5 has tumor-suppressing effects in many cancer types. For instance, in gastric cancer, its overexpression suppressed cell growth, migration, and invasion both in vitro and in a xenograft model, likely through inhibiting epithelial-mesenchymal transition (EMT) and inactivating MMP-2 and MMP-9 [1]. In bladder cancer, overexpression of Scara5 reduced cell viability, colony formation, invasion, and migration, and it was regulated by the PCAT29/miR-141 axis [4]. In oral squamous cell carcinoma, Scara5 overexpression inhibited cell proliferation, induced apoptosis, and repressed EMT by inactivating the STAT3 and PI3K/AKT signaling pathways [5]. In colorectal cancer, bone marrow stromal cell-derived exosomes containing Scara5 inhibited tumor growth and motility by inactivating the PI3K/Akt pathway [6]. In esophageal squamous cell carcinoma, Scara5 induced ferroptosis, suppressing cell cycle, metastasis, and invasion by combining with ferritin light chain [7]. In nasopharyngeal carcinoma, overexpression of Scara5 inhibited cell migration, invasion, and proliferation, and enhanced sensitivity to chemotherapy [8]. In melanoma, decreased Scara5 expression was associated with poor prognosis, and it was related to immune infiltration levels [9]. In colorectal cancer, low Scara5 expression was associated with poor prognosis, and its expression was negatively related to cell-cycle-associated gene sets [10]. Also, in prostate cancer, high Scara5 expression was associated with advanced tumor stage, positive nodal status, and high Gleason-score [3].

In conclusion, Scara5 appears to play a crucial role in tumorigenesis and cancer progression, acting as a potential tumor suppressor in multiple cancer types. Its role in these cancers, as revealed through in vitro and in vivo studies, provides valuable insights into cancer mechanisms and potential therapeutic targets. Additionally, in thrombosis and hemostasis, it may contribute to the clearance of VWF-FVIII, highlighting its significance in maintaining normal physiological function in the circulatory system [2].

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. 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/

3. 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/

4. 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/

5. 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/

6. 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/

7. 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/

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. 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/

10. 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/