کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10914529 | 1088792 | 2016 | 23 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Determination of cell uptake pathways for tumor inhibitor lysyl oxidase propeptide
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Determination of cell uptake pathways for tumor inhibitor lysyl oxidase propeptide Determination of cell uptake pathways for tumor inhibitor lysyl oxidase propeptide](/preview/png/10914529.png)
چکیده انگلیسی
The lysyl oxidase propeptide (LOX-PP) is derived from pro-lysyl oxidase (Pro-LOX) by extracellular biosynthetic proteolysis. LOX-PP inhibits breast and prostate cancer xenograft tumor growth and has tumor suppressor activity. Although, several intracellular targets and molecular mechanisms of action of LOX-PP have been identified, LOX-PP uptake pathways have not been reported. Here we demonstrate that the major uptake pathway for recombinant LOX-PP (rLOX-PP) is PI3K-dependent macropinocytosis in PWR-1E, PC3, SCC9, MDA-MB-231 cell lines. A secondary pathway appears to be dynamin- and caveola dependent. The ionic properties of highly basic rLOX-PP provide buffering capacity at both high and low pHs. We suggest that the buffering capacity of rLOX-PP, which serves to limit endosomal acidification, sustains PI3K-dependent macropinocytosis in endosomes which in turn is likely to facilitate LOX-PP endosomal escape into the cytoplasm and its observed interactions with cytoplasmic targets and nuclear uptake.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Oncology - Volume 10, Issue 1, January 2016, Pages 1-23
Journal: Molecular Oncology - Volume 10, Issue 1, January 2016, Pages 1-23
نویسندگان
Gokhan Baris Ozdener, Manish V. Bais, Philip C. Trackman,