Evidence map›Paper›PMID 30410397›Full record

ArticleCancer management and research2018

DJ-1 promotes survival of human colon cancer cells under hypoxia by modulating HIF-1α expression through the PI3K-AKT pathway.

Hong Zheng, Chao Zhou, Xiao Lu, Quanxing Liu, Minqiang Liu, Guoqing Chen, Weigang Chen, Shuai Wang, Yuan Qiu

Open access · goldAbstract read
In one paragraph

Article in Cancer management and research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.2field-weighted citation impact, top 24% of its field
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 32 citations in OpenAlex.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Hong ZhengDepartment of Thoracic Surgery of Xinqiao Hospital, The Third Military Medical University, Shapingba, 400037, Chongqing, People's Republic of China.
Chao ZhouDepartment of General Surgery of Xinqiao Hospital, The Third Military Medical University, Shapingba, 400037, Chongqing, People's Republic of China, xiaoq2037@126.com, wangshuaidoct@126.com.
Xiao LuDepartment of Thoracic Surgery of Xinqiao Hospital, The Third Military Medical University, Shapingba, 400037, Chongqing, People's Republic of China.
Quanxing LiuDepartment of Thoracic Surgery of Xinqiao Hospital, The Third Military Medical University, Shapingba, 400037, Chongqing, People's Republic of China.
Minqiang LiuDepartment of General Surgery of Xinqiao Hospital, The Third Military Medical University, Shapingba, 400037, Chongqing, People's Republic of China, xiaoq2037@126.com, wangshuaidoct@126.com.
Guoqing ChenDepartment of General Surgery of Xinqiao Hospital, The Third Military Medical University, Shapingba, 400037, Chongqing, People's Republic of China, xiaoq2037@126.com, wangshuaidoct@126.com.
Weigang ChenDepartment of General Surgery of Xinqiao Hospital, The Third Military Medical University, Shapingba, 400037, Chongqing, People's Republic of China, xiaoq2037@126.com, wangshuaidoct@126.com.
Shuai WangDepartment of General Surgery of Xinqiao Hospital, The Third Military Medical University, Shapingba, 400037, Chongqing, People's Republic of China, xiaoq2037@126.com, wangshuaidoct@126.com.
Yuan QiuDepartment of General Surgery of Xinqiao Hospital, The Third Military Medical University, Shapingba, 400037, Chongqing, People's Republic of China, xiaoq2037@126.com, wangshuaidoct@126.com.
Xinqiao Hospital · CNArmy Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundProtein/nucleic acid deglycase (DJ-1) and hypoxia-inducible factor-1α (HIF-1α) play significant roles in the progression of various types of cancer and are associated with the phosphatidylinositol 3-kinase (PI3K) pathway. However, their functions in colorectal cancer (CRC) have not been identified. The aim of this study was to analyze the putative signaling pathway encompassing DJ-1, PI3K, and HIF-1α in a series of CRC tissues and cell lines. PURPOSE: This study aimed at exploring the expression status of DJ-1 in colon cancer and its role in survival of cancer cell lines.

methodsThe expression and localization of DJ-1, PI3K-p110α, phosphorylated Akt (p-AKT), and HIF-1α were determined by immunohistochemistry in 73 resected CRC tissues. The effect of DJ-1 on cell activity was explored by in vitro knockdown and overexpression experiments in SW480 and HT-29 cells. The cells were treated with a PI3K inhibitor (LY294002 or wortmannin), and p-AKT and HIF-1α protein expression were then analyzed. Apoptosis was analyzed by flow cytometry. The expression levels of several HIF-1 target genes were assessed under hypoxic conditions by reverse transcription-PCR and Western blot. Xenograft tumor growth studies were conducted in DJ-1 knockdown or overexpression cells.

resultsHigh DJ-1 expression was found in 68.49% (50/73) of CRC tissues and associated with larger tumor size and advanced clinical stages. DJ-1 expression was positively associated with PI3K-p110α, p-AKT, and HIF-1α expression in CRC. HIF-1α and p-AKT protein levels were lower in SW480 and HT-29 cells with stable DJ-1 knockdown than in those with DJ-1 overexpression. PI3K inhibitors almost completely blocked DJ-1-induced AKT phosphorylation. However, the expression of HIF-1α was partially preserved after treatment with PI3K inhibitors. We also show that DJ-1 is necessary for the transcriptional ability of HIF-1α and CRC cell survival after hypoxic stress. Moreover, DJ-1 promoted the growth of established tumor xenografts in nude mice.

conclusionOur findings are the first to show that DJ-1 is overexpressed in CRC. We suggest a model in which DJ-1 mediates CRC cell survival by regulating the PI3K-AKT-HIF-1α pathway.

Indexed as

colorectal cancerDJ-1hypoxia-inducible factor-1αphosphatidylinositol 3-kinasephosphorylated Akt

Identifiers

PMID30410397
PMCPMC6199970
OpenAlexW2896809609

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.