Home > A. Molecular pathology > LATSs

LATSs

Wednesday 11 January 2017

Members

- LATS1
- LATS2

WKP

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.

Functions

- The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERα

  • 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.

See also

- LATSs
- LATS2
- Hippo pathway

Paywall references

- The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERα. 2016. doi : 10.1038/nature20829

See also

- Hippo pathway