Oxygen gradient and tumor heterogeneity: The chronicle of a toxic relationship
| Autor: | Sanjeev Shukla, Madhura R. Pandkar, Shruti Ganesh Dhamdhere |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Cell Communication Biology Tumor heterogeneity Epigenesis Genetic 03 medical and health sciences Genetic Heterogeneity 0302 clinical medicine Neoplasms Genetics medicine Basic Helix-Loop-Helix Transcription Factors Tumor Microenvironment Warburg Effect Oncologic Animals Humans Reverse Warburg effect Epigenetics Cancer epigenetics Tumor microenvironment Cancer Hypoxia (medical) medicine.disease Cell biology Gene Expression Regulation Neoplastic Oxygen 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell Tumor Hypoxia Hypoxia-Inducible Factor 1 medicine.symptom Signal Transduction |
| Zdroj: | Biochimica et biophysica acta. Reviews on cancer. 1876(1) |
| ISSN: | 1879-2561 |
| Popis: | The commencement of cancer is attributed to one or a few cells that become rogue and attain the property of immortality. The inception of distinct cancer cell clones during the hyperplastic and dysplastic stages of cancer progression is the utimate consequence of the dysregulated cellular pathways and the proliferative potential itself. Furthermore, a critical factor that adds a layer of complexity to this pre-existent intra-tumoral heterogeneity (ITH) is the foundation of an oxygen gradient, that is established due to the improper architecture of the tumor vasculature. Therefore, as a resultant effect, the poorly oxygenated regions thus formed and characterized as hypoxic, promote the emergence of aggressive and treatment-resistant cancer cell clones. The extraordinary property of the hypoxic cancer cells to exist harmoniously with cancerous and non-cancerous cells in the tumor microenvironment (TME) further increases the intricacies of ITH. Here in this review, the pivotal influence of differential oxygen concentrations in shaping the ITH is thoroughly discussed. We also emphasize on the vitality of the interacting networks that govern the overall fate of oxygen gradient-dependent origin of tumor heterogeneity. Additionally, the implications of less-appreciated reverse Warburg effect, a symbiotic metabolic coupling, and the associated epigenetic regulation of rewiring of cancer metabolism in response to oxygen gradients, have been highlighted as critical influencers of ITH. |
| Databáze: | OpenAIRE |
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