EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer
Open accessAbstract
Tumors are cellularly and molecularly heterogeneous, with subsets of undifferentiated cancer cells exhibiting stem cell-like features (CSCs). Epithelial to mesenchymal transitions (EMT) are transdifferentiation programs that are required for tissue morphogenesis during embryonic development. The EMT process can be regulated by a diverse array of cytokines and growth factors, such as transforming growth factor (TGF)-beta, whose activities are dysregulated during malignant tumor progression. Thus, EMT induction in cancer cells results in the acquisition of invasive and metastatic properties. Recent reports indicate that the emergence of CSCs occurs in part as a result of EMT, for example, through cues from tumor stromal components. Recent evidence now indicates that EMT of tumor cells not only causes increased metastasis, but also contributes to drug resistance. In this review, we will provide potential mechanistic explanations for the association between EMT induction and the emergence of CSCs. We will also highlight recent studies implicating the function of TGF-beta-regulated noncoding RNAs in driving EMT and promoting CSC self-renewal. Finally we will discuss how EMT and CSCs may contribute to drug resistance, as well as therapeutic strategies to overcome this clinically.
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EMT is a phenotype switching event induced by targeted therapy in various tumors that has been linked to drug tolerance and/or resistance.
“For instance, epithelial-to-mesenchymal transition (EMT) is a phenotype switching event induced by targeted therapy in various tumors that has been linked to drug tolerance and/or resistance [78,79].”
From Emerging Insights into Targeted Therapy-Tolerant Persister Cells in Cancer (2021) · cites this paper as [78]
Carcinoma cells undergoing EMT tend to be more resistant to chemotherapy.
“EMT also correlates with increased resistance of carcinoma cells to chemotherapies149–152.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [149]
High TGF-β signaling has been implicated in resistance to various anti-cancer treatments including chemotherapies and molecularly-targeted therapies.
“High TGF-β signaling has been implicated in resistance to various anti-cancer treatments including chemotherapies and molecularly-targeted therapies149,380,381.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [149]
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- Authors
- Singh, A., & Settleman, J.
- Affiliations
- Harvard University (US)
- Corresponding author
- Settleman, J
- ORCID
- Singh, A
- Venue
- Oncogene
- Published
- 2010-06-07
- Volume
- 29
- Issue
- 34
- Pages
- 4741-4751
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- PMC
- PMC3176718
- OpenAlex
- W2028593825
- Cited by
- 2,545
- References
- 102
- Citations by year
- 2026: 35 · 2025: 67 · 2024: 94 · 2023: 124 · 2022: 158 · 2021: 198 · 2020: 187 · 2019: 210 · 2018: 215 · 2017: 241 · 2016: 221 · 2015: 188 · 2014: 171 · 2013: 162 · 2012: 157
- FWCI
- 15.10
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (K99CA149169, R00CA149169)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mechanisms of cancer metastasis
- Keywords
- epithelial-mesenchymal transition, cancer stem cells, drug resistance, TGF-beta, non-coding RNA, tumor stroma, metastasis, self-renewal, tumor heterogeneity, cancer therapy resistance
- MeSH terms
- Animals, Epithelial Cells, Humans, Mesoderm, Neoplasms, Neoplastic Stem Cells, Drug Resistance, Neoplasm
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