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Investigating unstable chromosomes in cancer cells

  • Researcher: Dr Alexander Bird
  • Institution: Max Planck Institute, Dortmund, Germany
  • Award Amount: £189,163 for 3 years from 1st April 2016
  • Cancer Type: General Cancer Research
Investigating unstable chromosomes in cancer cells
A common characteristic of tumours is that their cells have the wrong number of chromosomes. Often, the numbers of chromosomes within tumour cells are constantly changing, a phenomenon termed “Chromosomal INstability” or “CIN”. CIN contributes to tumour progression, and the degree of CIN correlates with metastasis (the spreading of tumour cells in the body), resistance to therapy, and poor patient prognosis. It is thought that the changing genetic diversity that CIN provides allows tumours to grow, survive, and resist treatment.

Dr Alexander Bird explains “Our objective is to understand the molecular basis of how CIN arises in tumours, with hope that we can identify treatments to reduce CIN and tumor progression. We know that CIN can arise when cells incorrectly segregate (separate) chromosomes when the cells divide, but we do not have a good understanding of why these errors occur in tumours, in other words, the molecular basis for these defects.”

He continued “We have found a gene, GTSE1, whose overexpression (switched on to high levels) in tumours correlates with high tumour grade and therefore a poorer outcome for patients. When we reduce GTSE1 levels, the cancer cells have less chromosome segregation errors, suggesting an important role of GTSE1 in CIN. We have found that GTSE1 is required to control the function and dynamic nature of microtubules during cell division, which are required for the accurate segregation of chromosomes.

With this project we are aiming to demonstrate that GTSE1 levels influence CIN severity in tumour cells through regulation of microtubule dynamics. Support from Worldwide Cancer Research is allowing us to dig deeper into the detailed molecular mechanism by which loss of control of GTSE1 in cancer cells impacts microtubule dynamics and chromosomal instability, and importantly, show that we can reduce CIN in tumour cells by targeting GTSE1.”
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