Prolonged hypoxia promotes enrichment of cytosolic EZH2 in breast cancer stem cells via a HIF-1α-independent mechanism
Cancer stem cells (CSCs) make up a small subpopulation of the entire tumour. They have the ability to self-renew as well as differentiate into the cells that make up the bulk tumour. Previously, we have demonstrated that EZH2 is highly enriched in the cytosol of breast cancer stem cells (BCSCs), res...
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| Format: | Final Year Project (FYP) |
| Language: | English |
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Nanyang Technological University
2020
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| Online Access: | https://hdl.handle.net/10356/142015 |
| _version_ | 1826119052951552000 |
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| author | Law, Daniel Cheng Lui |
| author2 | Su I-Hsin |
| author_facet | Su I-Hsin Law, Daniel Cheng Lui |
| author_sort | Law, Daniel Cheng Lui |
| collection | NTU |
| description | Cancer stem cells (CSCs) make up a small subpopulation of the entire tumour. They have the ability to self-renew as well as differentiate into the cells that make up the bulk tumour. Previously, we have demonstrated that EZH2 is highly enriched in the cytosol of breast cancer stem cells (BCSCs), resulting in EZH2-dependent methylation of Talin1 and subsequent hyperactivation of STAT3. We also identified a subpopulation within BCSCs that highly expressed cytosolic EZH2 (60-80%). Since the tumour microenvironment has been revealed to be a suitable niche for CSCs, we sought to evaluate whether the hypoxic tumour microenvironment could result in further enrichment of cytosolic EZH2 in BCSCs. We discovered that our in vitro CSC-like model exhibited significantly higher cytosolic EZH2 under prolonged hypoxia in a HIF-1α-independent manner. Paradoxically, HIF-1α, EZH2 and STAT3 activation levels were decreased upon acute and prolonged hypoxia, indicating that HIF-2α may be responsible for the observed changes. The activation of PI3K-mTORC2 and biphasic activation pattern of ERK1/2 further supported the preference of HIF-2α over HIF-1α under prolonged hypoxia. In conclusion, this study highlighted a potential HIF-1α-independent hypoxic adaptive response which may have played a role in the further enrichment of cytosolic EZH2 in BCSCs. |
| first_indexed | 2024-10-01T04:53:44Z |
| format | Final Year Project (FYP) |
| id | ntu-10356/142015 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:53:44Z |
| publishDate | 2020 |
| publisher | Nanyang Technological University |
| record_format | dspace |
| spelling | ntu-10356/1420152023-02-28T18:07:57Z Prolonged hypoxia promotes enrichment of cytosolic EZH2 in breast cancer stem cells via a HIF-1α-independent mechanism Law, Daniel Cheng Lui Su I-Hsin School of Biological Sciences IHSu@ntu.edu.sg Science::Biological sciences::Molecular biology Cancer stem cells (CSCs) make up a small subpopulation of the entire tumour. They have the ability to self-renew as well as differentiate into the cells that make up the bulk tumour. Previously, we have demonstrated that EZH2 is highly enriched in the cytosol of breast cancer stem cells (BCSCs), resulting in EZH2-dependent methylation of Talin1 and subsequent hyperactivation of STAT3. We also identified a subpopulation within BCSCs that highly expressed cytosolic EZH2 (60-80%). Since the tumour microenvironment has been revealed to be a suitable niche for CSCs, we sought to evaluate whether the hypoxic tumour microenvironment could result in further enrichment of cytosolic EZH2 in BCSCs. We discovered that our in vitro CSC-like model exhibited significantly higher cytosolic EZH2 under prolonged hypoxia in a HIF-1α-independent manner. Paradoxically, HIF-1α, EZH2 and STAT3 activation levels were decreased upon acute and prolonged hypoxia, indicating that HIF-2α may be responsible for the observed changes. The activation of PI3K-mTORC2 and biphasic activation pattern of ERK1/2 further supported the preference of HIF-2α over HIF-1α under prolonged hypoxia. In conclusion, this study highlighted a potential HIF-1α-independent hypoxic adaptive response which may have played a role in the further enrichment of cytosolic EZH2 in BCSCs. Bachelor of Science in Biological Sciences 2020-06-15T02:38:53Z 2020-06-15T02:38:53Z 2020 Final Year Project (FYP) https://hdl.handle.net/10356/142015 en application/pdf Nanyang Technological University |
| spellingShingle | Science::Biological sciences::Molecular biology Law, Daniel Cheng Lui Prolonged hypoxia promotes enrichment of cytosolic EZH2 in breast cancer stem cells via a HIF-1α-independent mechanism |
| title | Prolonged hypoxia promotes enrichment of cytosolic EZH2 in breast cancer stem cells via a HIF-1α-independent mechanism |
| title_full | Prolonged hypoxia promotes enrichment of cytosolic EZH2 in breast cancer stem cells via a HIF-1α-independent mechanism |
| title_fullStr | Prolonged hypoxia promotes enrichment of cytosolic EZH2 in breast cancer stem cells via a HIF-1α-independent mechanism |
| title_full_unstemmed | Prolonged hypoxia promotes enrichment of cytosolic EZH2 in breast cancer stem cells via a HIF-1α-independent mechanism |
| title_short | Prolonged hypoxia promotes enrichment of cytosolic EZH2 in breast cancer stem cells via a HIF-1α-independent mechanism |
| title_sort | prolonged hypoxia promotes enrichment of cytosolic ezh2 in breast cancer stem cells via a hif 1α independent mechanism |
| topic | Science::Biological sciences::Molecular biology |
| url | https://hdl.handle.net/10356/142015 |
| work_keys_str_mv | AT lawdanielchenglui prolongedhypoxiapromotesenrichmentofcytosolicezh2inbreastcancerstemcellsviaahif1aindependentmechanism |