Investigating the role of MCL-1 in breast cancer stem cells

Prof Karen Blyth and Dr Kirsteen Campbell, Transgenic Models of Cancer

Annually, breast cancer accounts for over 11,000 deaths in the UK. We have found that high levels of MCL-1 (a pro-survival BCL-2 family member) at diagnosis predicts poor prognosis in breast cancer. Targeting MCL-1 has the potential to improve the treatment of breast cancer, particularly in subtypes that currently have limited treatment options (Campbell et al., 2018). Drugs specifically targeting MCL-1 have entered clinical trials with a focus on haematopoietic disease, and pre-clinical work suggests MCL-1 inhibitors could improve breast cancer outcome.

To enable the targeting of MCL-1 in the clinic, it is important to determine the role and requirement of MCL-1 at different breast cancer disease stages. In particular, we have identified a requirement for MCL-1 in breast cancer stem cells and a PhD studentship is available within the Transgenic Models of Cancer Lab to investigate the role of MCL-1 in breast cancer stem cells. Cells with stem-like properties are responsible for tumour initiation, metastatic spread and resistance to therapy. We wish to understand the role of MCL-1 in these processes and impact of targeting MCL-1.

The successful student will have the opportunity to work with primary mammary epithelial and tumour cells in 2D and 3D assays including stem cell assays; genetically engineered mouse models of breast cancer and a variety of techniques such as FACS and RNA-seq. Thus the student will gain experience and be trained in a range of leading edge techniques currently used in cancer research in a stimulating research environment.

For informal enquiries or further details on the project, please email Prof Karen Blyth (karen.blyth@glasgow.ac.uk)

To apply, please complete a PhD Studentship Form (in right-hand menu opposite). Application deadline: 3rd January 2020

 

References

Campbell et al., MCL-1 is a prognostic indicator and drug target in breast cancer. (2018) Cell Death Dis. 16;9(2):19

Campbell and Tait. Targeting BCL-2 regulated apoptosis in cancer. (2018) Open Biol. 8(5): 180002.

Lee et al., MYC and MCL1 Cooperatively Promote Chemotherapy-Resistant Breast Cancer Stem Cells via Regulation of Mitochondrial Oxidative Phosphorylation. (2017) Cell Metabolism. 26:633-647.

Merino et al., Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer. (2017) Science Translational Medicine. 2017;9(401) eaam7049.

Kotschy et al., The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. (2016) Nature 538(7626):477-82.

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