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Tunicamycin interferes with WNT signaling and inhibits angiogenesis
Author(s) -
Cruz Melanie
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03470
Subject(s) - tunicamycin , wnt signaling pathway , angiogenesis , cell growth , microbiology and biotechnology , signal transduction , chemistry , cell cycle , biology , cancer research , cell , unfolded protein response , biochemistry , endoplasmic reticulum
Wnt signaling pathway is a family of proteins that can lead to a cascade of cell proliferation. The transcription co‐activator β‐catenin has been associated with the development of tissue. Recent studies have shown that Wnt signaling have a significant role in vascular development, an important event in tumor growth. Therefore, it regulates some biological processes (i.e. cell proliferation, apoptosis). Our laboratory has established that protein N‐glycosylation inhibitor Tunicamycin reduces angiogenesis. It also reduces the progression of double negative (ER ‐ /PR ‐ /HER2 + ) and triple negative (ER ‐ /PR ‐ /HER2 ‐ ) breast tumor growth in athymic nude mice. Tunicamycin is a competitive inhibitor of N‐acetylglucosaminyl 1‐phosphate transferase (GPT) activity and down regulates Glc 3 Man 9 GlcNAc 2 ‐PP‐Dol biosynthesis. The consequence is “ER stress“ and the cell cycle arrest in G1. This led us to hypothesize that decreased expression of Wnt protein(s) in Tunicamycin treated endothelial cell would decrease the cell proliferation and angiogenesis. We have used in vitro culture of capillary endothelial cells as model and western blotting, and immunofluorescence microscopy as tools, and observed down regulated expression of Wnt proteins. We, therefore, concluded that Tunicamycin‐induced ER stress interferes with the Wnt signaling and inhibits angiogenesis. This study helps us to give explanations on how the Wnt signaling reacts in the presence of Tunicamycin. Also, leads us to think in his possible apoptotic potential.