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Can upside down cell division promote cancer development?

  • Researcher: Dr Angeliki Malliri
  • Institution: University of Manchester, Manchester, England
  • Award Amount: £203,518 for 3 years from 1st January 2016
  • Cancer Type: General Cancer Research
Can upside down cell division promote cancer development?
Dr Angeliki Malliri is studying why it is so important that cells grow and divide in the correct direction/orientation. Many tissues, such as kidney, breast and lung, consist of hollow spheres surrounded by a single layer of cells. New cells form side-by-side in the tissue. Potentially, if new cells form above or below the tissue layer, this may contribute to tumour formation. Many questions remain about the process for orientating cell divisions (so new cells know to grow side by side and not up or down).

Dr Malliri explains “We have recently identified a role for the protein CASK in this process. When CASK is depleted in normal kidney or breast cells, cell divisions are misorientated, and astral microtubules (the molecular cables within the cell which help orient cell divisions) are fewer and shorter. These cells then divide to form spheres with multiple centres - reminiscent of an early stage of breast cancer. Reintroducing CASK protein back into these cells restores normal spheres with single centres. To better understand how these abnormal structures form, we will use state-of-the-art microscopes to image live cells containing fluorescent proteins and watch as they form normal and abnormal spheres.

Another protein, Dlg1, whose loss causes tumour growth in other biological models and which binds CASK, is reduced when CASK is depleted. We will investigate whether depletion of Dlg1 gives rise to abnormal structures and misorientated divisions. We will also study how CASK is able to stabilise Dlg1 and investigate the importance of their binding.

To address the role of CASK in tumour formation and progression, we will examine human breast cancer tissues for reduced CASK and Dlg1 levels. Moreover, we will see whether breast cells with reduced CASK are more able to form tumours when introduced into mouse models.”
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