Evidence map›Paper›PMID 39358564›Full record

ArticleCancer gene therapy2024

Targeting CREB-binding protein (CBP) abrogates colorectal cancer stemness through epigenetic regulation of C-MYC.

Dai-Jung Chung, Chun-Hao Wang, Pin-Jung Liu, Shang-Kok Ng, Cong-Kai Luo, Si-Han Jwo, Chin-Tzu Li, Dai-Yi Hsu, Chia-Chu Fan, Tzu-Tang Wei

Abstract read
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Article in Cancer gene therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

10 authors.

Dai-Jung Chung *Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
Chun-Hao Wang *Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
Pin-Jung Liu *Department and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
Shang-Kok NgDepartment and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
Cong-Kai LuoDepartment and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
Si-Han JwoDepartment and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
Chin-Tzu LiDepartment and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
Dai-Yi HsuDepartment and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
Chia-Chu FanDepartment and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan.
Tzu-Tang WeiDepartment and Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, 10051, Taiwan. ttwei@ntu.edu.tw.ORCID 0000-0002-5751-4374

Funding

Ministry of Science and Technology, Taiwan (Ministry of Science and Technology of Taiwan) 109CFA0100103, 111CFA0100039, and 112-2320-B-002-028-MY3NTU | College of Medicine, National Taiwan University (College of Medicine, National Taiwan University) 111L4000 and 112L4000).
6 · The paper itself

Abstract

Colorectal cancer (CRC) is a common cancer worldwide with an increasing annual incidence. Cancer stem cells (CSCs) play important roles in the occurrence, development, recurrence, and metastasis of CRC. The molecular mechanism regulating the development of colorectal CSCs remains unclear. The discovery of human induced pluripotent stem cells (hiPSCs) through somatic cell reprogramming has revolutionized the fields of stem cell biology and translational medicine. In the present study, we converted hiPSCs into cancer stem-like cells by culture with conditioned medium (CM) from CRC cells. These transformed cells, termed hiPSC-CSCs, displayed cancer stem-like properties, including a spheroid morphology and the expression of both pluripotency and CSC markers. HiPSC-CSCs showed tumorigenic and metastatic abilities in mouse models. The epithelial-mesenchymal transition phenotype was observed in hiPSC-CSCs, which promoted their migration and angiogenesis. Interestingly, upregulation of C-MYC was observed during the differentiation of hiPSC-CSCs. Mechanistically, CREB binding protein (CBP) bound to the C-MYC promoter, while histone deacetylase 1 and 3 (HDAC1/3) dissociated from the promoter, ultimately leading to an increase in histone acetylation and C-MYC transcriptional activation during the differentiation of hiPSC-CSCs. Pharmacological treatment with a CBP inhibitor or abrogation of CBP expression with a CRISPR/Cas9-based strategy reduced the stemness of hiPSC-CSCs. This study demonstrates for the first time that colorectal CSCs can be generated from hiPSCs. The upregulation of C-MYC via histone acetylation plays a crucial role during the conversion process. Inhibition of CBP is a potential strategy for attenuating the stemness of colorectal CSCs.

Indexed as

Colorectal NeoplasmsCREB-Binding ProteinEpigenesis, GeneticNeoplastic Stem CellsProto-Oncogene Proteins c-mycAnimalsCell Line, TumorEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticHumansInduced Pluripotent Stem CellsMiceCREB-Binding ProteinCREBBP protein, humanMYC protein, humanProto-Oncogene Proteins c-myc

Identifiers

PMID39358564

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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.