{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSUSD2 is a type I transmembrane protein characterized by adhesion domains and initially identified in breast cancer, where it interacts with partners such as galectin‐1 to mediate cell–cell interactions. Its expression is generally low in normal epithelia but becomes upregulated in malignant lesions, suggesting a role in tumor initiation and progression. In addition, genomic studies have implicated SUSD2 as part of susceptibility loci in diseases such as amyotrophic lateral sclerosis, highlighting its diverse involvement in human pathology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn several solid tumors, such as breast and ovarian cancers, SUSD2 appears to promote tumor progression. In breast cancer, it facilitates cell invasion, enhances immune evasion, and contributes to angiogenesis by regulating the surface localization of galectin‐1 and inducing chemokine (MCP‐1) secretion that attracts tumor-associated macrophages. Similarly, in ovarian cancer, differential SUSD2 expression modulates platelet activation and cell–platelet adhesion, further influencing metastatic potential. Conversely, in renal cell and lung cancers, reduced SUSD2 levels have been associated with enhanced proliferation and clonogenicity, indicative of a tumor-suppressive function in these contexts. In gastric and endometrial cancers, higher SUSD2 expression correlates with increased malignant behavior and metastasis, emphasizing its context-dependent roles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nPost‐transcriptional and epigenetic mechanisms further regulate SUSD2 expression in various diseases. In glioma, for example, a circular RNA (circTOP2A) acts as a competing endogenous RNA to upregulate SUSD2 by sponging microRNA‑346, thereby enhancing tumor aggressiveness. Similarly, in contexts such as pneumonia and retinoblastoma, the interplay among long noncoding RNAs (SNHG16), microRNAs (miR‑141‑3p), and SUSD2 modulates cell apoptosis, autophagy, and angiogenesis. Moreover, in hepatocellular carcinoma, interactions with tropomyosin alpha‑4 (TPM4) potentially influence SUSD2 function, while in ovarian carcinoma, transcriptional repression of SUSD2 by CBX8 in complex with SET underscores its role in tumor cell growth and migration. Notably, SUSD2 also serves as a consistent marker for cultured human cardiac fibroblasts and myofibroblasts, reflecting its broader biological significance."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "10", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Allison P Watson, Rick L Evans, Kristi A Egland "}, {"type": "b", "children": [{"type": "t", "text": "Multiple functions of sushi domain containing 2 (SUSD2) in breast tumorigenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-12-0501-T"}], "href": "https://doi.org/10.1158/1541-7786.MCR-12-0501-T"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23131994"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23131994"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Min Deng, Ling Wei, Xianbo Zuo, et al. 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