A243: YAP/TAZ oncoproteins in epithelial stem cells and cancerThe YAP/TAZ family of transcriptional co-activators were originally discovered by Drosophila genetics, and are now emerging as potent regulators of stem cell proliferation and tumour formation.  I will discuss how YAP/TAZ proteins are regulated during normal epithelial homeostasis and during tumour formation and progression to malignancy.  Our primary hypothesis is that YAP/TAZ proteins act as sensors of apical and basolateral polarity cues that then control the subcellular localisation of YAP/TAZ.  In stem cells, which generally lack an apical domain but are in contact with the basement membrane, YAP/TAZ proteins are nuclear and promote cell proliferation.  Similarly, loss of the apical domain during the adenoma to carcinoma transition leads to strongly nuclear YAP/TAZ localisation.  The molecular mechanisms controlling YAP/TAZ localisation will be discussed, as will conditional mouse knockouts for YAP and TAZ in epithelia.

Barry Thompson1

1Francis Crick Institute, London, UK

Presenting date: Monday 2 November
Presenting time: 12.20-13.10

Background

The YAP/TAZ family of transcriptional co-activators were originally discovered by Drosophila genetics, and are now emerging as potent regulators of stem cell proliferation and tumour formation.

Method

I will discuss how YAP/TAZ proteins are regulated during normal epithelial homeostasis and during tumour formation and progression to malignancy.

Results

Our primary hypothesis is that YAP/TAZ proteins act as sensors of apical and basolateral polarity cues that then control the subcellular localisation of YAP/TAZ.  In stem cells, which generally lack an apical domain but are in contact with the basement membrane, YAP/TAZ proteins are nuclear and promote cell proliferation.  Similarly, loss of the apical domain during the adenoma to carcinoma transition leads to strongly nuclear YAP/TAZ localisation.  The molecular mechanisms controlling YAP/TAZ localisation will be discussed, as will conditional mouse knockouts for YAP and TAZ in epithelia.

Conclusion

We conclude that YAP/TAZ proteins sense apical and basolateral polarity inputs to control cell proliferation in epithelial stem cells and cancer.