Evidence map›Paper›PMID 39079386›Full record

ArticleRedox biology2024

Hypoxia-induced cysteine metabolism reprogramming is crucial for the tumorigenesis of colorectal cancer.

Zhang Lin, Shiyi Yang, Qianqian Qiu, Gaoping Cui, Yanhua Zhang, Meilian Yao, Xiangyu Li, Chengkun Chen, Jun Gu, Ting Wang and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Redox biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
–field-weighted citation impact
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

31 citing papers in PubMed.

  1. Article
  2. The emerging roles of disulfidptosis in cancer.Apoptosis : an international journal on programmed cell death · 2026
    Review
  3. Targeting glutathione metabolism for tumor radiosensitization (Review).International journal of molecular medicine · 2026
    Review
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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

13 authors.

Zhang LinState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Shiyi YangState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Qianqian QiuState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China; Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University Medical School Cancer Institute, Tongji University School of Medicine, Shanghai, 200433, China.
Gaoping CuiState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Yanhua ZhangState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Meilian YaoState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Xiangyu LiState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Chengkun ChenState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Jun GuState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Ting WangState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China.
Peng YinKey Laboratory of Chemical Biology and Traditional Chinese Medicine Research, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, 410081, China.
Longci SunState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China; Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: renjisunlongci@163.com.
Yujun HaoState Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Renji Hospital, School of Biomedical Engineering, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200032, China. Electronic address: yjhao@shsci.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Metabolic reprogramming is a hallmark of human cancer, and cancer-specific metabolism provides opportunities for cancer diagnosis, prognosis, and treatment. However, the underlying mechanisms by which metabolic pathways affect the initiation and progression of colorectal cancer (CRC) remain largely unknown. Here, we demonstrate that cysteine is highly enriched in colorectal tumors compared to adjacent non-tumor tissues, thereby promoting tumorigenesis of CRC. Synchronously importing both cysteine and cystine in colorectal cancer cells is necessary to maintain intracellular cysteine levels. Hypoxia-induced reactive oxygen species (ROS) and ER stress regulate the co-upregulation of genes encoding cystine transporters (SLC7A11, SLC3A2) and genes encoding cysteine transporters (SLC1A4, SLC1A5) through the transcription factor ATF4. Furthermore, the metabolic flux from cysteine to reduced glutathione (GSH), which is critical to support CRC growth, is increased due to overexpression of glutathione synthetase GSS in CRC. Depletion of cystine/cysteine by recombinant cyst(e)inase effectively inhibits the growth of colorectal tumors by inducing autophagy in colorectal cancer cells through mTOR-ULK signaling axis. This study demonstrates the underlying mechanisms of cysteine metabolism in tumorigenesis of CRC, and evaluates the potential of cysteine metabolism as a biomarker or a therapeutic target for CRC.

Indexed as

Colorectal NeoplasmsCysteineMetabolic ReprogrammingActivating Transcription Factor 4Amino Acid Transport System ASCAmino Acid Transport System y+AnimalsCarcinogenesisCell Line, TumorCystineEndoplasmic Reticulum StressGene Expression Regulation, NeoplasticGlutathioneHumansHypoxiaMiceActivating Transcription Factor 4Amino Acid Transport System ASCAmino Acid Transport System y+CysteineCystineGlutathioneMinor Histocompatibility AntigensReactive Oxygen SpeciesSLC1A5 protein, humanSLC7A11 protein, humanATF4Colorectal cancerCysteine/cystineHypoxiaROS homeostasisTransporter genes

Identifiers

PMID39079386
PMCPMC11340627

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Registered trials

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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.