Evidence map›Paper›PMID 42283915›Full record

ArticleMolecular biomedicine2026

TELO2-interacting protein 1 (TTI1), a novel Wnt/β-catenin target gene, decreases chemo-sensitivity in colorectal cancer by modulating DNA damage responses.

Yuqiao Chen, Zheng Chen, Ya Wang, Yuanbing Yao, Youyu Zhang, Wentao Huang, Kun Song, Fengbo Tan, Fei Long, Changwei Lin and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular biomedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

17 authors.

Yuqiao Chen *Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zheng Chen *Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Ya WangInstitute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Yuanbing YaoInstitute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Youyu ZhangDepartment of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Wentao HuangDepartment of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Kun SongDepartment of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Fengbo TanDepartment of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Fei LongDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Changwei LinDepartment of Gastrointestinal Surgery, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Qian ZhangDepartment of Nutrition and Health, China Agricultural University, Beijing, China.
Wei ZhuDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, China.
Wei ZhuangDepartment of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Jianhua ZhouDepartment of Pathology, Xiangya Hospital, Central South University, Changsha, China.
Heli LiuDepartment of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Shuai XiaoHengyang Medical School, The First Affiliated Hospital, Cancer Research Institute, University of South China, Hengyang, Hunan, China.
Kai FuInstitute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. fu_kai@csu.edu.cn.ORCID http://orcid.org/0000-0001-8571-5352

Funding

Department of Science and Technology of Hunan Province 2025JK2135Department of Science and Technology of Hunan Province 2026JJ20031National Natural Science Foundation of China 32170726
6 · The paper itself

Abstract

Colorectal cancer is frequently driven by hyperactivation of Wnt/β-catenin signaling, which also contributes to reduced responsiveness to chemotherapy. However, how aberrant Wnt/β-catenin signaling enables colorectal cancer cells to tolerate chemotherapy-induced DNA damage remains elusive. Identifying actionable downstream effectors of this pathway may provide a more selective strategy to improve chemotherapy response while avoiding the toxicity associated with global Wnt inhibition. Here we show that TELO2-interacting protein 1 (TTI1) is a direct transcriptional target of β-catenin/TCF in colorectal cancer. TTI1 expression correlates with β-catenin abundance and is elevated in tumors from patients with poor response to neoadjuvant chemotherapy. Mechanistically, TTI1 maintains the integrity of the TELO2-TTI1-TTI2 complex and stabilizes the DNA damage response kinases ATM and ATR. Genetic depletion of TTI1 destabilizes ATM and ATR, attenuates DNA damage signaling, impairs double-strand break repair, and sensitizes colorectal cancer cells to 5-fluorouracil and oxaliplatin. Conversely, restoration of TTI1 or ATM/ATR re-establishes DNA damage responses and chemo-insensitivity. Pharmacological suppression of the TTT complex by piperlongumine mimics TTI1 loss and enhances the anti-tumor activity of chemotherapy in cell lines, xenografts, Apc-mutant patient-derived organoids and Apc

Indexed as

beta CateninColorectal NeoplasmsDNA-Binding ProteinsDNA DamageDrug Resistance, NeoplasmWnt Signaling PathwayAnimalsAtaxia Telangiectasia Mutated ProteinsCell Line, TumorDNA RepairGene Expression Regulation, NeoplasticHumansMiceAtaxia Telangiectasia Mutated Proteinsbeta CateninDNA-Binding ProteinsChemo-sensitivityColorectal CancerDNA Damage ResponseWnt/β-catenin Signaling

Identifiers

PMID42283915
PMCPMC13263369

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.