{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMUC15 is a membrane‐associated mucin with diverse roles in cancer biology. In several tumor types including colorectal adenocarcinoma, glioma, pancreatic cancer, and hepatocellular carcinoma, aberrant MUC15 expression is linked to enhanced malignant features such as increased cellular proliferation, adhesion, invasion, and resistance to chemotherapy. In colorectal tumors, for example, MUC15 overexpression augments cell–extracellular matrix adhesion and invasion through activation of ERK1/2 signaling, whereas in gliomas and pancreatic ductal adenocarcinoma similar overexpression correlates with aggressive tumor progression and poor clinical outcome. Notably, in hepatocellular carcinoma and renal cell carcinoma, decreased MUC15 in specific tumor‐initiating or normal tissues is associated with the loss of its inhibitory influence on PI3K/AKT and related pathways, evidencing its context‐dependent role as either an oncogene or tumor suppressor. These contrasting observations highlight MUC15’s complex influence on tumorigenesis and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic studies have further delineated the pathways underlying MUC15’s dualistic functions. In papillary thyroid carcinoma, for instance, MUC15 expression levels were evaluated alongside other molecular markers to assess its prognostic relevance. Similarly, in gastrointestinal cancers with microsatellite instability, frameshift mutations and regional heterogeneity in the MUC15 gene correlate with loss of protein expression, implying that genetic alterations may modulate its biological effects. These investigations underscore that MUC15 influences tumor progression via key signaling cascades including ERK, PI3K/AKT, and GSK3β/β‐catenin, and that its mutation status can serve as a biomarker for disease aggressiveness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond oncology, MUC15 also plays roles in non‐malignant processes. In placental biology, studies have shown that MUC15 is expressed in the human placenta and may act to restrain trophoblast invasion, a key event in placental development. Complementary investigations into mucin gene profiles in epithelial tissues such as the larynx, as well as genetic studies linking mucin‐related loci with conditions like eczema, further suggest that MUC15 contributes to the maintenance of epithelial barriers and selective signaling in both normal physiology and pathological conditions including preeclampsia. These findings imply that MUC15 has broader implications in epithelial homeostasis and stem cell biology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "John Huang, Mei-Ieng Che, Yu-Ting Huang, et al. 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