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- W3134720901 abstract "The proapoptotic, antiangiogenic, and antimetastatic activities of insulin-like growth factor binding protein-3 (IGFBP-3) through IGF-dependent or -independent mechanisms have been suggested in various types of human cancers. However, a mechanistic explanation of and downstream targets involved in the antimetastatic effect of IGFBP-3 is still lacking. In this study, by applying various in vitro and in vivo models, we show that IGFBP-3 suppresses migration and invasion of human head and neck squamous carcinoma (HNSCC) and non-small cell lung cancer (NSCLC) cells. Silencing IGFBP-3 expression elevated the migration and invasion of NSCLC and HNSCC cells in vitro and their local invasion and metastasis in vivo, whereas overexpression of IGFBP-3 decreased such prometastatic changes. Local invasion of 4-nitroquinoline-1-oxide (4-NQO)-induced HNSCC tumors was consistently significantly potentiated in Igfbp3 knockout mice compared with that in wild-type mice. Mechanistically, IGFBP-3 disrupted the protein stability of vimentin via direct binding and promoting its association with the E3 ligase FBXL14, causing proteasomal degradation. The C-terminal domain of IGFBP-3 and the head domain of vimentin are essential for their interaction. These results provide a molecular framework for IGFBP-3′s IGF-independent antimetastatic and antitumor activities." @default.
- W3134720901 created "2021-03-15" @default.
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- W3134720901 creator A5061505466 @default.
- W3134720901 creator A5070372188 @default.
- W3134720901 creator A5080743502 @default.
- W3134720901 date "2021-03-02" @default.
- W3134720901 modified "2023-09-27" @default.
- W3134720901 title "Insulin-Like Growth Factor Binding Protein-3 Exerts Its Anti-Metastatic Effect in Aerodigestive Tract Cancers by Disrupting the Protein Stability of Vimentin" @default.
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- W3134720901 doi "https://doi.org/10.3390/cancers13051041" @default.
- W3134720901 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7958122" @default.
- W3134720901 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33801272" @default.
- W3134720901 hasPublicationYear "2021" @default.
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