{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZG16B, also known as pancreatic adenocarcinoma upregulated factor (PAUF), is a secreted lectin-like protein that exhibits a Jacalin-related β-prism fold. Crystallographic studies have revealed that its putative sugar‐binding site–in conjunction with an adjacent basic patch–facilitates binding to glycosaminoglycans. This structural arrangement not only underlies its physiological role in the condensation–sorting of pancreatic enzymes (as seen with its paralog ZG16p) but also enables recognition of specific glycoconjugates, a property further exemplified by its ability to bind microbial glycans in the oral cavity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its structural features, ZG16B/PAUF functions as a potent oncoprotein that modulates key intracellular signaling pathways. It engages Toll-like receptors—particularly TLR2 and TLR4—to activate downstream effectors such as extracellular signal–regulated kinase (ERK), while simultaneously upregulating chemokine receptors like CXCR4. These events trigger cascades that enhance tumor cell proliferation, migration, invasion, and metastasis. In pancreatic and colorectal cancer models, PAUF has been shown to stabilize β-catenin via Akt and GSK-3β modulation, further promoting cell cycle progression and chemoresistance. In addition, PAUF can enhance cell adhesion through activation of focal adhesion kinase (FAK), thereby contributing to a more aggressive tumor phenotype."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its direct effects on tumor cells, ZG16B/PAUF exerts significant paracrine influences on the tumor microenvironment. It promotes angiogenesis and increases vascular permeability by activating ERK, AKT, and endothelial nitric oxide synthase (eNOS) in endothelial cells, with concomitant upregulation of CXCR4 that potentiates the angiogenic response. Moreover, PAUF modulates antitumor immunity by recruiting and functionally activating myeloid-derived suppressor cells (MDSCs) through TLR4-mediated signaling, thereby contributing to immune evasion. Its systemic effects extend to the induction of cancer cachexia via muscle atrophy and may even alter the sensitivity of cancer cells to oncolytic viral therapies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "18"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mayumi Kanagawa, Tadashi Satoh, Akemi Ikeda, et al. 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