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Hypoxia Induces Growth Differentiation Factor 15 to Promote the Metastasis of Colorectal Cancer via PERK-eIF2α Signaling
Joint Authors
Zheng, Hongtu
Wu, Yuchen
Guo, Tianan
Liu, Fangqi
Xu, Ye
Cai, Sanjun
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-01-29
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Zheng, Hongtu& Wu, Yuchen& Guo, Tianan& Liu, Fangqi& Xu, Ye& Cai, Sanjun. 2020. Hypoxia Induces Growth Differentiation Factor 15 to Promote the Metastasis of Colorectal Cancer via PERK-eIF2α Signaling. BioMed Research International،Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1135119
Modern Language Association (MLA)
Zheng, Hongtu…[et al.]. Hypoxia Induces Growth Differentiation Factor 15 to Promote the Metastasis of Colorectal Cancer via PERK-eIF2α Signaling. BioMed Research International No. 2020 (2020), pp.1-12.
https://search.emarefa.net/detail/BIM-1135119
American Medical Association (AMA)
Zheng, Hongtu& Wu, Yuchen& Guo, Tianan& Liu, Fangqi& Xu, Ye& Cai, Sanjun. Hypoxia Induces Growth Differentiation Factor 15 to Promote the Metastasis of Colorectal Cancer via PERK-eIF2α Signaling. BioMed Research International. 2020. Vol. 2020, no. 2020, pp.1-12.
https://search.emarefa.net/detail/BIM-1135119
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1135119