Abstract:
:Hypoxia plays an essential role in orchestrating Epithelial-mesenchymal transition and promoting metastasis of colorectal cancer. However, the underlying mechanisms are still not well elucidated. Here, we present that hypoxic exposure causes endoplasmic reticulum stress and activates the unfolded protein response pathways, which drives GDF15 expression in colorectal cancer cells. Mechanistically, upregulated CHOP led by activated PERK-eIF2α signaling promotes GDF15 transcription via directly binding to its promoter. Further study implicates that hypoxia-induced GDF15 is required for the EMT and invasion of colorectal cancer cells; enforced expression of GDF15 promotes the mitochondrial oxidation of fatty acids in colorectal cancer cells. Moreover, the abrogation of GDF15 results in smaller xenograft tumors in size and impaired metastasis. GDF15 is expressed much more in tumor tissues of CRC patients and displays positive correlations with CHOP and HIF1α in mRNA levels. Our study demonstrates a novel molecular mechanism underlying hypoxia-promoted metastasis of CRC and provides PERK signaling-regulated GDF15 as a new and promising therapeutic target for clinical treatment and drug discovery.
journal_name
Biomed Res Intjournal_title
BioMed research internationalauthors
Zheng H,Wu Y,Guo T,Liu F,Xu Y,Cai Sdoi
10.1155/2020/5958272subject
Has Abstractpub_date
2020-01-27 00:00:00pages
5958272eissn
2314-6133issn
2314-6141journal_volume
2020pub_type
杂志文章abstract:Aims:To investigate demographics and socioeconomic status in patients with ulnar nerve compression and the influence of socioeconomic factors on patient-reported outcome measurements (PROM) as evaluated by QuickDASH (short version of Disabilities of Arm, Shoulder and Hand) after surgery for ulnar nerve compression at t...
journal_title:BioMed research international
pub_type: 杂志文章
doi:10.1155/2020/5928649
更新日期:2020-12-18 00:00:00
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journal_title:BioMed research international
pub_type: 杂志文章
doi:10.1155/2020/3593962
更新日期:2020-12-11 00:00:00
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journal_title:BioMed research international
pub_type: 杂志文章
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journal_title:BioMed research international
pub_type: 杂志文章,评审
doi:10.1155/2020/8234618
更新日期:2020-12-09 00:00:00
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journal_title:BioMed research international
pub_type: 杂志文章
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journal_title:BioMed research international
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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journal_title:BioMed research international
pub_type: 杂志文章
doi:10.1155/2020/6692802
更新日期:2020-12-09 00:00:00
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pub_type: 杂志文章
doi:10.1155/2018/3817057
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pub_type: 杂志文章
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pub_type: 杂志文章
doi:10.1155/2018/8367068
更新日期:2018-03-26 00:00:00
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journal_title:BioMed research international
pub_type: 杂志文章
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journal_title:BioMed research international
pub_type: 杂志文章
doi:10.1155/2016/9140541
更新日期:2016-01-01 00:00:00
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journal_title:BioMed research international
pub_type: 杂志文章
doi:10.1155/2020/6096280
更新日期:2020-12-29 00:00:00
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journal_title:BioMed research international
pub_type: 杂志文章,评审
doi:10.1155/2014/841798
更新日期:2014-01-01 00:00:00
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journal_title:BioMed research international
pub_type: 杂志文章
doi:10.1155/2014/480498
更新日期:2014-01-01 00:00:00
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journal_title:BioMed research international
pub_type: 杂志文章
doi:10.1155/2016/5682541
更新日期:2016-01-01 00:00:00
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journal_title:BioMed research international
pub_type: 杂志文章,评审
doi:10.1155/2017/9217145
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journal_title:BioMed research international
pub_type: 杂志文章,meta分析
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journal_title:BioMed research international
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doi:10.1155/2020/3967427
更新日期:2020-12-04 00:00:00
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pub_type: 杂志文章
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journal_title:BioMed research international
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更新日期:2020-10-10 00:00:00
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journal_title:BioMed research international
pub_type: 杂志文章
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更新日期:2013-01-01 00:00:00
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journal_title:BioMed research international
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pub_type: 杂志文章,评审
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