NDLI: The unfolded protein response potentiates epithelial-to-mesenchymal transition (EMT) of gastric cancer cells under severe hypoxic conditions

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The unfolded protein response potentiates epithelial-to-mesenchymal transition (EMT) of gastric cancer cells under severe hypoxic conditions

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Shen, Xinsheng Xue, Yange Si, Yaqing Wang, Qun Wang, Zhao Yuan, Jiaxiang Zhang, Xiefu
Description	Country affiliation: China Author Affiliation: Shen X ( Department of Minimally Invasive Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, 450052, Henan, China.)
Abstract	The hypoxic condition occurs in most types of solid tumors and has been shown to be associated with the metastatic ability of gastric cancer. A previous study has demonstrated that hypoxia might stimulate epithelial-to-mesenchymal transition (EMT) of gastric cancer cells. Nevertheless, the mechanism has not yet been completely understood. In the current study, the human gastric cancer cell lines HGC27 and MGC803 were presented to normoxic (21 % $O_{2}),$ hypoxic (1 % $O_{2})$ or severe hypoxic (0.1 % $O_{2})$ conditions for 24 h. We found that hypoxia exposure induced EMT of gastric cancer cells, which was promoted by severe hypoxia condition. Meanwhile, expressions of PERK, ATF4 and ATF6 proteins were elevated in cells under conditions of severe hypoxia but not by normoxia or hypoxia. Knockdown of PERK, ATF4 or ATF6 impeded EMT of gastric cancer cells induced by severe hypoxia. Furthermore, severe hypoxia exposure extremely boosted the expression of TGF-β, which was blocked by the knockdown of PERK, ATF4 or ATF6 expression. Additionally, we found that TGF-β release caused by hypoxia is facilitated by elevated UPR proteins and led to the activation of Smad2/3 and PI3K/Akt signaling. Our data suggest that UPR potentiates the EMT of gastric cancer cells under conditions of severe hypoxia.
File Format	HTM / HTML
ISSN	13570560
Issue Number	1
Volume Number	32
e-ISSN	1559131X
Journal	Medical Oncology
Language	English
Publisher	Springer
Publisher Date	2015-01-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Rna, Small Interfering Humans Unfolded Protein Response Blotting, Western Enzyme-linked Immunosorbent Assay Journal Article Gene Knockdown Techniques Cell Hypoxia Pathology Cell Line, Tumor Physiology Stomach Neoplasms Discipline Oncology Epithelial-mesenchymal Transition
Content Type	Text
Resource Type	Article
Subject	Hematology Cancer Research Oncology

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