Evidence map›Paper›PMID 30068339›Full record

ArticleJournal of biomedical science2018

STAT3 exacerbates survival of cancer stem-like tumorspheres in EGFR-positive colorectal cancers: RNAseq analysis and therapeutic screening.

Chun-Chia Cheng, Po-Nien Liao, Ai-Sheng Ho, Ken-Hong Lim, Jungshan Chang, Ying-Wen Su, Caleb Gon-Shen Chen, Ya-Wen Chiang, Bi-Ling Yang, Huan-Chau Lin and 3 more

Abstract read
In one paragraph

Article in Journal of biomedical science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
–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

22 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  8. Cancer chemoprevention: signaling pathways and strategic approaches.Signal transduction and targeted therapy · 2025
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  15. Fermented kimchi rejuvenated precancerous atrophic gastritis via mitigatingJournal of clinical biochemistry and nutrition · 2021
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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.

Chun-Chia ChengDivision of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Po-Nien LiaoDivision of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Ai-Sheng HoDivision of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan.
Ken-Hong LimDivision of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Jungshan ChangGraduate Institute of Medical Sciences, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Ying-Wen SuDivision of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Caleb Gon-Shen ChenDivision of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Ya-Wen ChiangDivision of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Bi-Ling YangDivision of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan.
Huan-Chau LinDivision of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Yu-Cheng ChangDivision of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
Chun-Chao ChangDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan. chunchao@tmu.edu.tw.
Yi-Fang ChangDivision of Hematology and Oncology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan. changyifang@gmail.com.

Funding

Ministry of Science and Technology, Taiwan MOST 106-2320-B-038 -048Ministry of Science and Technology, Taiwan MOST 106-2320-B195-003
6 · The paper itself

Abstract

backgroundCancer stem cells are capable of undergoing cell division after surviving cancer therapies, leading to tumor progression and recurrence. Inhibitory agents against cancer stem cells may be therapeutically used for efficiently eradicating tumors. Therefore, the aim of this study was to identify the relevant driver genes that maintain cancer stemness in epidermal growth factor receptor (EGFR)-positive colorectal cancer (CRC) cells and to discover effective therapeutic agents against these genes.

methodsIn this study, EGFR-positive cancer stem-like cells (CSLCs) derived from HCT116 and HT29 cells were used as study models for in vitro inductions. To identify the differential genes that maintain CSLCs, RNAseq analysis was conducted followed by bioinformatics analysis. Moreover, a panel containing 172 therapeutic agents targeting the various pathways of stem cells was used to identify effective therapeutics against CSLCs.

resultsRNAseq analysis revealed that 654 and 840 genes were significantly upregulated and downregulated, respectively, in the HCT116 CSLCs. Among these genes, notably, platelet-derived growth factor A (PDGFA) and signal transducer and activator of transcription 3 (STAT3) were relevant according to the cancer pathway analyzed using NetworkAnalyst. Furthermore, therapeutic screening revealed that the agents targeting STAT3 and Wnt signaling pathways were efficient in reducing the cell viabilities of both HCT116 and HT29 cells. Consequently, we discovered that STAT3 inhibition using homoharringtonine and STAT3 knockdown significantly reduced the formation and survival of HT29-derived tumorspheres. We also observed that STAT3 phosphorylation was regulated by epidermal growth factor (EGF) to induce PDGFA and Wnt signaling cascades.

conclusionsWe identified the potential genes involved in tumorsphere formation and survival in selective EGFR-positive CRCs. The results reveal that the EGF-STAT3 signaling pathway promotes and maintains CRC stemness. In addition, a crosstalk between STAT3 and Wnt activates the Wnt/β-catenin signaling pathway, which is also responsible for cancer stemness. Thus, STAT3 is a putative therapeutic target for CRC treatment.

Indexed as

Colorectal NeoplasmsEarly Detection of CancerEpidermal Growth FactorErbB ReceptorsGene Expression Regulation, NeoplasticHT29 CellsHumansNeoplastic Stem CellsPhosphorylationPlatelet-Derived Growth FactorSequence Analysis, RNASTAT3 Transcription FactorWnt Signaling PathwayEGFR protein, humanEpidermal Growth FactorErbB ReceptorsPlatelet-Derived Growth Factorplatelet-derived growth factor ASTAT3 protein, humanSTAT3 Transcription FactorCancer stem cellEGFRLGR5PDGFASTAT3Wnt

Identifiers

PMID30068339
PMCPMC6090986

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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.