Evidence map›Paper›PMID 35973989›Full record

ArticleSignal transduction and targeted therapy2022

DDX39B drives colorectal cancer progression by promoting the stability and nuclear translocation of PKM2.

Gang Zhao, Hang Yuan, Qin Li, Jie Zhang, Yafei Guo, Tianyu Feng, Rui Gu, Deqiong Ou, Siqi Li, Kai Li and 1 more

Open access · goldAbstract read
In one paragraph

Article in Signal transduction and targeted therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
11.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

76 citing papers in PubMed, 126 citations in OpenAlex.

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16 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Gang Zhao *Lab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Hang Yuan *Lab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Qin LiLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Jie ZhangLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Yafei GuoLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Tianyu FengLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Rui GuLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Deqiong OuLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Siqi LiLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Kai LiLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. likai@wchscu.cn.
Ping LinLab of Experimental Oncology, State Key Laboratory of Biotherapy and Cancer Center, and Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China. linping@scu.edu.cn.ORCID 0000-0001-8982-8397
Sichuan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metastasis is a major cause of colorectal cancer (CRC) mortality, but its molecular mechanisms are still not fully understood. Here, we show that upregulated DDX39B correlates with liver metastases and aggressive phenotypes in CRC. DDX39B is an independent prognostic factor associated with poor clinical outcome in CRC patients. We demonstrate that Sp1 potently activates DDX39B transcription by directly binding to the GC box of the DDX39B promoter in CRC cells. DDX39B overexpression augments the proliferation, migration, and invasion of CRC cells, while the opposite results are obtained in DDX39B-deficient CRC cells. Mechanistically, DDX39B interacts directly with and stabilizes PKM2 by competitively suppressing STUB1-mediated PKM2 ubiquitination and degradation. Importantly, DDX39B recruits importin α5 to accelerate the nuclear translocation of PKM2 independent of ERK1/2-mediated phosphorylation of PKM2, leading to the transactivation of oncogenes and glycolysis-related genes. Consequently, DDX39B enhances glucose uptake and lactate production to activate Warburg effect in CRC. We identify that Arg319 of DDX39B is required for PKM2 binding as well as PKM2 nuclear accumulation and for DDX39B to promote CRC growth and metastasis. In addition, blocking PKM2 nuclear translocation or treatment with glycolytic inhibitor 2-deoxy-D-glucose efficiently abolishes DDX39B-triggered malignant development in CRC. Taken together, our findings uncover a key role for DDX39B in modulating glycolytic reprogramming and aggressive progression, and implicate DDX39B as a potential therapeutic target in CRC.

Indexed as

Carrier ProteinsColorectal NeoplasmsDEAD-box RNA HelicasesGlycolysisMembrane ProteinsThyroid HormonesCell Line, TumorHumansPhosphorylationProtein TransportThyroid Hormone-Binding ProteinsUbiquitin-Protein LigasesCarrier ProteinsDDX39B protein, humanDEAD-box RNA HelicasesMembrane ProteinsSTUB1 protein, humanThyroid Hormone-Binding ProteinsThyroid HormonesUbiquitin-Protein Ligases

Identifiers

PMID35973989
PMCPMC9381590
OpenAlexW4293277975

What OpenQuestion holds

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LicenceCC BY
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.