{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMajor vault protein (MVP), the principal component of vault ribonucleoprotein complexes, has emerged as a multifunctional regulator in cancer biology. In colon cancer cells, MVP mediates the selective export of tumor‐suppressive miR‑193a via exosomes, thereby depleting the donor cells’ inhibitory signals and promoting tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Its expression—as often measured under the designation “lung resistance‐related protein” (LRP)—has been linked to drug resistance and adverse clinical outcomes in various malignancies including breast cancer, acute myeloid leukemia, and non–small cell lung cancer, where differential regulation and hypoxia‐induced upregulation further correlate with poor prognosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "8"}]}, {"type": "t", "text": " Moreover, MVP expression is subject to regulation by p53 via a mechanism involving Y‑box binding protein 1, further intertwining its role with therapeutic resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Notably, some studies have also reported that, in certain tumor models, a direct role for MVP in multidrug resistance is not observable, highlighting the complexity of its functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its involvement in chemoresistance, MVP functions as a versatile molecular scaffold that modulates several key signaling pathways. It acts as a substrate for the tyrosine phosphatase SHP‑2, thereby facilitating epidermal growth factor (EGF)–induced extracellular signal–regulated kinase (ERK) activation and promoting cell survival."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " MVP also directly interacts with the tumor suppressor PTEN in a calcium‐dependent manner, influencing its nucleocytoplasmic distribution and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Furthermore, via its association with Src family kinases—accompanied by EGF‐triggered subcellular translocation—MVP modulates downstream mitogenic signals."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " In glioblastoma, MVP stabilizes the EGFR/phosphatidylinositol‑3‑kinase (PI3K) axis to enhance invasion and survival"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ", while in triple‐negative breast cancer, Notch1‐driven MVP expression amplifies AKT activation and fosters epithelial–mesenchymal transition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " In chondrosarcoma, MVP was recently shown to bind GLI1, impeding its interaction with the suppressor SUFU and thereby promoting Hedgehog pathway activation via the mTOR/S6K1 cascade."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMVP’s functions extend into innate immunity and cellular stress responses. 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