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Cited by 50Cancer Cells and MetastasisCancer, Hypoxia, and MetabolismTGF-β signaling in diseases

Cancer stem cells, epithelial-mesenchymal transition, ATP and their roles in drug resistance in cancer

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Zhang, Haiyun, Steed, Alexander, Co, Milo, Chen, Xiaozhuo·2021·Cancer Drug Resistance
DOI 10.20517/cdr.2021.32PMC PMC8315560
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Abstract

The cancer stem cell (CSC) state and epithelial-mesenchymal transition (EMT) activation are tightly interconnected. Cancer cells that acquire the EMT/CSC phenotype are equipped with adaptive metabolic changes to maintain low reactive oxygen species levels and stemness, enhanced drug transporters, anti-apoptotic machinery and DNA repair system. Factors present in the tumor microenvironment such as hypoxia and the communication with non-cancer stromal cells also promote cancer cells to enter the EMT/CSC state and display related resistance. ATP, particularly the high levels of intratumoral extracellular ATP functioning through both signaling pathways and ATP internalization, induces and regulates EMT and CSC. The three of them work together to enhance drug resistance. New findings in each of these factors will help us explore deeper into mechanisms of drug resistance and suggest new resistance-associated markers and therapeutic targets.

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200 of 209 shown

Cited by

Sorted by citations

Authors
Zhang, H., Steed, A., Co, M., & Chen, X.
Affiliations
Ohio University (US)
Corresponding author
Chen, Xiaozhuo
ORCID
Venue
Cancer Drug Resistance
Publisher
OAE Publishing Inc.
Published
2021
Volume
4
Pages
684-709
ISSN
2578-532X (ISSN-L)
DOI
10.20517/cdr.2021.32
PMC
PMC8315560
OpenAlex
W3175570129
Cited by
50
References
10
Citations by year
2026: 6 · 2025: 14 · 2024: 9 · 2023: 14 · 2022: 7
FWCI
2.73
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Cancer Drug Resistance (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Cancer Institute (R15CA242177)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
cancer stem cells, epithelial-mesenchymal transition, extracellular ATP, drug resistance, tumor microenvironment, hypoxia, reactive oxygen species, drug transporters, DNA repair, ATP signaling, resistance markers, therapeutic target

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