Self-Renewal and Pluripotency in Osteosarcoma Stem Cells' Chemoresistance: Notch, Hedgehog, and Wnt/β-Catenin Interplay with Embryonic Markers.
Sara R Martins-NevesGabriela Sampaio-RibeiroCélia M F GomesPublished in: International journal of molecular sciences (2023)
Osteosarcoma is a highly malignant bone tumor derived from mesenchymal cells that contains self-renewing cancer stem cells (CSCs), which are responsible for tumor progression and chemotherapy resistance. Understanding the signaling pathways that regulate CSC self-renewal and survival is crucial for developing effective therapies. The Notch, Hedgehog, and Wnt/β-Catenin developmental pathways, which are essential for self-renewal and differentiation of normal stem cells, have been identified as important regulators of osteosarcoma CSCs and also in the resistance to anticancer therapies. Targeting these pathways and their interactions with embryonic markers and the tumor microenvironment may be a promising therapeutic strategy to overcome chemoresistance and improve the prognosis for osteosarcoma patients. This review focuses on the role of Notch, Hedgehog, and Wnt/β-Catenin signaling in regulating CSC self-renewal, pluripotency, and chemoresistance, and their potential as targets for anti-cancer therapies. We also discuss the relevance of embryonic markers, including SOX-2, Oct-4, NANOG, and KLF4, in osteosarcoma CSCs and their association with the aforementioned signaling pathways in overcoming drug resistance.
Keyphrases
- cancer stem cells
- stem cells
- cell proliferation
- signaling pathway
- induced apoptosis
- epithelial mesenchymal transition
- end stage renal disease
- transcription factor
- pi k akt
- ejection fraction
- cell therapy
- endoplasmic reticulum stress
- bone marrow
- newly diagnosed
- prognostic factors
- squamous cell carcinoma
- oxidative stress
- diabetic retinopathy
- climate change
- radiation therapy
- risk assessment
- patient reported
- poor prognosis