Determination of cell uptake pathways for tumor inhibitor lysyl oxidase propeptide

作者: Gokhan Baris Ozdener , Manish V. Bais , Philip C. Trackman

DOI: 10.1016/J.MOLONC.2015.07.005

关键词:

摘要: The lysyl oxidase propeptide (LOX-PP) is derived from pro-lysyl (Pro-LOX) by extracellular biosynthetic proteolysis. LOX-PP inhibits breast and prostate cancer xenograft tumor growth has suppressor activity. Although, several intracellular targets molecular mechanisms of action have been identified, uptake pathways not reported. Here we demonstrate that the major pathway for recombinant (rLOX-PP) PI3K-dependent macropinocytosis in PWR-1E, PC3, SCC9, MDA-MB-231 cell lines. A secondary appears to be dynamin- caveola dependent. ionic properties highly basic rLOX-PP provide buffering capacity at both high low pHs. We suggest rLOX-PP, which serves limit endosomal acidification, sustains endosomes turn likely facilitate escape into cytoplasm its observed interactions with cytoplasmic nuclear uptake.

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