Abstract
Cellular plasticity can occur naturally in an organism and is considered an adapting mechanism during the developmental stage. However, abnormal cellular plasticity is observed in different diseased conditions, including cancer. Cancer cell plasticity triggers the stimuli of epithelial-mesenchymal transition (EMT), abnormal epigenetic changes, expression of stem cell factors and implicated signaling pathways, etc., and helps in the maintenance of CSC phenotype. Conversely, CSC maintains the cancer cell plasticity, EMT, and epigenetic plasticity. EMT contributes to increased cell migration and greater diversity within tumors, while epigenetic changes, stem cell factors (OCT4, NANOG, and SOX2), and various signaling pathways allow cancer cells to maintain various phenotypes, giving rise to intra- and inter-tumoral heterogeneity. The intricate relationships between cancer cell plasticity and stem cell factors help the tumor cells adopt drug-tolerant states, evade senescence, and successfully acquire drug resistance with treatment dismissal. Inhibiting molecules/signaling pathways involved in promoting CSCs, cellular plasticity, EMT, and epigenetic plasticity might be helpful for successful cancer therapy management. This review discussed the role of cellular plasticity, EMT, and stem cell factors in tumor initiation, progression, reprogramming, and therapy resistance. Finally, we discussed how the intervention in this axis will help better manage cancers and improve patient survivability.
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Abbreviations
- AKT:
-
Protein kinase B
- BCRP:
-
Breast cancer resistance protein
- CSC:
-
Cancer stem cells
- CaP:
-
Prostate cancer
- DVL:
-
Dishevelled
- EGFR:
-
Epidermal growth factor receptor
- ESC:
-
Epithelial stem cells
- EMT:
-
Epithelial-mesenchymal transition
- FOXC1:
-
Forkhead box c1
- FZ:
-
Frizzled
- HIF:
-
Hypoxia-induced factor
- IL:
-
Interleukin
- JAK:
-
Janus kinase
- KLF4:
-
Krüppel-like factor
- KRAS:
-
Kirsten rat sarcoma
- MRP1:
-
Multidrug resistance protein 1
- OCT4:
-
Octamer-binding transcription factor 4
- P-gp:
-
P-glycoprotein
- PI3K:
-
PhosphatidylInositol 3-kinase
- ROS:
-
Reactive oxygen species
- STAT:
-
Signal transducer and activator of transcription
- SMO:
-
Smoothened
- SOX:
-
SRY-related HMG-box
- TGF:
-
Tumor growth factor
- TKI:
-
Tyrosine kinase inhibitor
- ZEB:
-
Zinc finger transcription factor
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Acknowledgements
The authors are thankful to Aligarh Muslim University, India, for providing the necessary facilities. HF expresses her sincere gratitude for the fellowship to UGC (F.82-27/2019(SA-III)), India. HRS is grateful to The UGC (Grant no.F.30-377/2017(BSR)) and DST-SERB (Grant no. EMR/2017/001758), New Delhi, India, for providing financial help.
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Fatma, H., Siddique, H.R. Cancer cell plasticity, stem cell factors, and therapy resistance: how are they linked?. Cancer Metastasis Rev 43, 423–440 (2024). https://doi.org/10.1007/s10555-023-10144-9
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DOI: https://doi.org/10.1007/s10555-023-10144-9