Evidence map›Paper›PMID 39773485›Full record

ArticleCell communication and signaling : CCS2025

FOXC1-mediated serine metabolism reprogramming enhances colorectal cancer growth and 5-FU resistance under serine restriction.

Zhukai Chen, Jiacheng Xu, Kang Fang, Hanyu Jiang, Zhuyun Leng, Hao Wu, Zehua Zhang, Zeyu Wang, Zhaoxing Li, Mingchuang Sun and 8 more

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2025. 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
–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

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Crosstalk between mFrontiers in immunology · 2026
    Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
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

18 authors.

Zhukai Chen *Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Jiacheng Xu *Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Kang Fang *Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Hanyu Jiang *Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Zhuyun LengEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Hao WuEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Zehua ZhangEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Zeyu WangEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Zhaoxing LiEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Mingchuang SunEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Ziying ZhaoEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Anqi FengEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Shihan ZhangEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Yuan ChuEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Lechi YeDepartment of Colorectal Surgery, Zhongshan Hospital, Fudan University, Shanghai, China. ye.lechi@zs-hospital.sh.cn.
Meidong XuEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China. 1800512@tongji.edu.cn.
Lingnan HeEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China. 2205551@tongji.edu.cn.
Tao ChenEndoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China. chentao@tongji.edu.cn.

Funding

Fundamental Research Funds for the Central Universities 22120240372National Natural Science Foundation of China 82172816National Natural Science Foundation of China 82372921Shanghai Municipal Health Commission 20224Z0016
6 · The paper itself

Abstract

Colorectal cancer (CRC) is the most common gastrointestinal malignancy, and 5-Fluorouracil (5-FU) is the principal chemotherapeutic drug used for its treatment. However, 5-FU resistance remains a significant challenge. Under stress conditions, tumor metabolic reprogramming influences 5-FU resistance. Serine metabolism plasticity is one of the crucial metabolic pathways influencing 5-FU resistance in CRC. However, the mechanisms by which CRC modulates serine metabolic reprogramming under serine-deprived conditions remain unknown. We found that exogenous serine deprivation enhanced the expression of serine synthesis pathway (SSP) genes, which in turn supported CRC cell growth and 5-FU resistance. Serine deprivation activate the ERK1/2-p-ELK1 signaling axis, leading to upregulated FOXC1 expression in CRC cells. Elevated FOXC1 emerged as a critical element, promoting the transcription of serine metabolism enzymes PHGDH, PSAT1, and PSPH, which in turn facilitated serine production, supporting CRC growth. Furthermore, through serine metabolism, FOXC1 influenced purine metabolism and DNA damage repair, thereby increasing 5-FU resistance. Consequently, combining dietary serine restriction with targeted therapy against the ERK1/2-pELK1-FOXC1 axis could be a highly effective strategy for treating CRC, enhancing the efficacy of 5-FU.

Indexed as

Cell ProliferationColorectal NeoplasmsDrug Resistance, NeoplasmFluorouracilForkhead Transcription FactorsSerineAnimalsCell Line, TumorGene Expression Regulation, NeoplasticHumansMetabolic ReprogrammingMiceMice, NudeFluorouracilForkhead Transcription FactorsFOXC1 protein, humanSerine5-Fluorouracil resistanceColorectal cancerDe novo serine synthesisFOXC1Metabolic reprogramming

Identifiers

PMID39773485
PMCPMC11708197

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.