Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is among the most frequently inactivated tumour suppressor genes in sporadic cancer, including breast cancer. This project aims to investigate the role of SGLT1 in the pathogenesis of PTEN-inactive breast cancer using cell biology, proteomics and biochemistry analysis.
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is among the most frequently inactivated tumour suppressor genes in sporadic cancer, including breast cancer. However, no pharmacologic approaches to restore PTEN protein directly have yet succeeded. It would thus be particularly important to gain further insights into the signaling pathway of PTEN loss as these efforts may be translated into a targeted therapy against cancers with those mutations, which would maximize efficacy while minimizing toxicity. To comprehensively identify therapeutic targets for PTEN-inactive breast cancer, a whole-genome high-throughput RNA interference screen for synthetic lethality with PTEN loss was set up in Julian Downward’s lab (Wang Y et al., unpublished data). This screen enabled us to find Sodium/glucose cotransporter 1 (SGLT1) as a potential therapeutic target for PTEN-inactive breast cancer. This project aims to investigate the role of SGLT1 in the pathogenesis of PTEN-inactive breast cancer using cell biology, proteomics and biochemistry analysis. Specifically, we aim to (i) elucidate biological and molecular changes following SGLT1 inhibition or depletion in PTEN-inactive breast cancer; (ii) map protein‐protein interaction networks to generate the first comprehensive map of SGLT1 protein interactions in PTEN-inactive breast cancer; (iii) assess selected interacting partners in functional studies using knockdown, inhibitors and immuno-co-localization approaches. This project is specifically designed to provide a wide‐ranging training programme that addresses current skills gaps in systems and quantitative biology approaches and their application to significant medical challenges. We will provide the student with a comprehensive training in molecular and cellular biology, and the cutting‐edge proteomic techniques, analysis and integration of large‐scale ‘omics’ datasets. This training will take place in an active and energetic community of researchers at Southampton of biomedical researchers, bioinformaticians and computer scientists, with the support from scientists in the Francis Crick Institute.
Principle Investigator (PI): Dr Yihua Wang
Secondary Supervisors: Dr Rob Ewing & Julian Downward
Funding: Wessex Medical Research
Funding Duration: October 2017-September 2021