Wednesday 11 January 2017
Serine/threonine-protein kinase LATS1 is an enzyme that in humans is encoded by the LATS1 gene. It has been associated with the Hippo pathway.
- Cell fate perturbations underlie many human diseases, including breast cancer.
- Unfortunately, the mechanisms by which breast cell fate are regulated are largely unknown.
- The mammary gland epithelium consists of differentiated luminal epithelial and basal myoepithelial cells, as well as undifferentiated stem cells and more restricted progenitors.
- Breast cancer originates from this epithelium, but the molecular mechanisms that underlie breast epithelial hierarchy remain ill-defined.
- Ablation of the large tumour suppressor kinases (LATS1 and LATS2 , which are part of the Hippo pathway, promotes the luminal phenotype and increases the number of bipotent and luminal progenitors, the proposed cells-of-origin of most human breast cancers.
- Mechanistically, authors have identified a direct interaction between Hippo and oestrogen receptor-α (ERα) signalling.
- In the presence of LATS, ERα was targeted for ubiquitination and Ddb1–cullin4-associated-factor 1 (DCAF1)-dependent proteasomal degradation.
- Absence of LATS stabilized ERα and the Hippo effectors YAP and TAZ (hereafter YAP/TAZ), which together control breast cell fate through intrinsic and paracrine mechanisms.
- It is a non-canonical, YAP /TAZ -independent, effect of LATSs in the regulation of human breast cell fate.
The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERα. 2016. doi : 10.1038/nature20829