Regulation of Sox2 by Ionizing Radiation

• Author / Creator

  Wu, Min Hsuan

• Within a tumour, only a subset of cells are able to initiate neoplasms when transplanted or following localization to different organs. These tumour-initiating cells, often called cancer stem cells (CSCs) due to their high cellular plasticity, were found to exhibit particular resistance to genotoxic therapies. They are also thought to be the primary cause of local recurrence and metastasis. CSCs display characteristics similar to those of induced-pluripotent stem cells, namely their ability to self-renew and potential to differentiate. The transcription factor Sox2 is an essential gene involved in stem cell maintenance as well as the establishment of induced-pluripotency and cancer stem cell phenotypes. Moreover, its amplification is detected in multiple cancers and has been linked to a more invasive phenotype. Recent studies suggest that some DNA damaging cancer therapies and hypoxia can trigger dedifferentiation and an increase in cancer stem cell populations associated with elevated Sox2 levels. However the mechanism of Sox2 induction remains unclear. Contrary to previous reports, our studies indicate that ionizing radiation (IR) leads to down-regulation of Sox2 protein in cancer cell lines – this regulation occurred post-transcriptionally and is dependent on ATM activation. Using a Sox2 reporter cell line, we observed that while Sox2 protein decreases with IR, there is an induction of Sox2 activity with increasing IR dose which was further augmented when combined with hypoxia. Many cancers are characterized by hierarchical cell populations, with CSCs displaying high self renewal and differentiation capacity. Radiotherapy is a common treatment modality and has been shown to promote a CSC phenotype in surviving cells. Our studies show that Sox2 protein stability and transcriptional activity are altered by radiation treatment in vitro. Understanding whether regulation of Sox2 by IR has the potential to impact cancer cell fate and identifying the regulatory factors involved may provide a basis for designing novel targeted therapies and improving cancer outcome.

• Subjects / Keywords

  • ionizing radiation
  • Cancer stem cells
  • Sox2

• Graduation date

  Fall 2019

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-k48t-1w60

• License

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