Evidence map›Paper›PMID 41882103›Full record

ArticleOncogene2026

ZDHHC9-mediated KLF5 palmitoylation enhances the cAMP/PKA/CREB axis to promote colorectal cancer progression.

Hao Zhang, Yuan Tian, Zeyu Xiang, Feng Han, Miaomiao Chen, Chunhui Jiang, Ye Liu, Hanbing Xue, Lipeng Hu, Chunjie Xu and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 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

12 authors.

Hao Zhang *Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
Yuan Tian *Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
Zeyu Xiang *Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
Feng Han *Department of Oncology, Lianyungang Oriental Hospital, Lianyungang, 222042, Jiangsu Province, China.
Miaomiao Chen *Department of Radiology, Huashan Hospital, National Center for Neurological Disorders, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200040, China.
Chunhui JiangDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
Ye LiuDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China.
Hanbing XueDivision of Gastroenterology and Hepatology; Key Laboratory of Gastroenterology and Hepatology, Ministry of Health; Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. medxue@126.com.ORCID http://orcid.org/0000-0002-6579-3625
Lipeng HuState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China. lphu@shsci.org.ORCID http://orcid.org/0000-0002-5941-3825
Chunjie XuDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. renjixuchunjie@163.com.
Lei GuDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. renjigulei@163.com.ORCID http://orcid.org/0000-0001-5119-3517
Qing XuDepartment of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Road, Shanghai, 200127, China. renjixuqing@163.com.ORCID http://orcid.org/0000-0002-1052-5666

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82303214National Natural Science Foundation of China (National Science Foundation of China) 82372878
6 · The paper itself

Abstract

S-palmitoylation, a reversible lipid-based post-translational modification, is notably elevated in colorectal cancer (CRC) due to common lipid metabolism disorders. It has been reported to play crucial roles in regulating membrane composition, cell proliferation, and metastasis in various malignancies such as pancreatic and breast cancers. However, its role in the progression of CRC remains poorly understood. ZDHHC9, a member of the palmitoyl transferase family, is significantly upregulated in CRC patients and correlates with poor prognosis. Knockdown of ZDHHC9 impairs CRC cell proliferation and migration both in vitro and in vivo. RNA sequencing revealed that ZDHHC9 depletion markedly downregulates the cAMP signaling pathway. Mechanistically, ZDHHC9 knockdown impairs ADCY4 activity by reducing S-palmitoylation of KLF5 at cysteine 438, thereby modulating the ZDHHC9/KLF5/ADCY4 axis and downstream cAMP/PKA/CREB signaling to influence CRC cell proliferation and migration. Our findings demonstrate that ZDHHC9 promotes CRC progression by regulating intracellular cAMP levels through KLF5 palmitoylation, providing a novel therapeutic perspective targeting palmitoylation in CRC. The mechanism diagram of this study. ZDHHC9 mediates palmitoylation of KLF5 at cysteine 438, thereby enhancing ADCY4 activity and increasing intracellular cAMP levels. This elevation in cAMP promotes PKA and phosphorylation of CREB, ultimately activating the cAMP/PKA/CREB signaling pathway, which contributes to the regulation of CRC cell proliferation, migration, and resistance to 5-FU. (Created with BioRender.com).

Indexed as

AcyltransferasesColorectal NeoplasmsCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinKruppel-Like Transcription FactorsAnimalsCell Line, TumorCell MovementCell ProliferationDisease ProgressionGene Expression Regulation, NeoplasticHumansLipoylationMiceSignal TransductionAcyltransferasesCREB1 protein, humanCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinKLF5 protein, humanKruppel-Like Transcription Factors

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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.