Advances in studying the role of SCARA5 in tumors

Scavenger receptor class A member 5 (SCARA5), a type II transmembrane glycoprotein, initially drew attention due to its involvement in iron metabolism and immune defense. In recent years, its tumor-suppressive function has been gradually validated in a variety of malignant tumors. SCARA5 is localized to the chromosomal region 8p21.1, a site with a high frequency of loss of heterozygosity (LOH) in tumors. Additionally, the high methylation of CpG islands in the SCARA5 promoter region, regulation by transcription factors, and post-transcriptional silencing mediated by non-coding RNAs (ncRNAs) collectively result in a significant downregulation of SCARA5 expression in tumors such as liver cancer, breast cancer, and colorectal cancer. Functionally, SCARA5 exerts multiple tumor-suppressive effects, including inhibiting tumor cell proliferation, inducing apoptosis, blocking epithelial-mesenchymal transition (EMT), and enhancing ferroptosis sensitivity. It achieves these effects by interacting with molecules such as FAK and ferritin to regulate signaling pathways like PI3K/Akt and Wnt/β-catenin. Furthermore, the expression level of SCARA5 is closely associated with tumor stage, lymph node metastasis, and patient prognosis, indicating its potential as a marker for tumor diagnosis and prognosis. Gene therapy, the application of DNA methyltransferase inhibitors (DNMTi), and the development of small-molecule drugs based on its regulatory mechanisms also offer new directions for precision tumor therapy. This article systematically reviews the gene and protein structure of SCARA5, its tumor-related mechanisms of action, expression regulatory network, and clinical translational value. It also analyzes current research gaps to provide references for future in-depth exploration.