Send to

Choose Destination
Life Sci Alliance. 2018 Oct 30;1(5):e201800171. doi: 10.26508/lsa.201800171. eCollection 2018 Oct.

LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state.

Author information

Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Laboratory of Histology and Embryology Medical School, University of Athens, Athens, Greece.
Department of Life Sciences Core Facilities, Faculty of Biochemistry, Weizmann Institute of Science, Rehovot, Israel.
Department of Cancer Biology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.


Deregulated activity of LArge Tumor Suppressor (LATS) tumor suppressors has broad implications on cellular and tissue homeostasis. We examined the consequences of down-regulation of either LATS1 or LATS2 in breast cancer. Consistent with their proposed tumor suppressive roles, expression of both paralogs was significantly down-regulated in human breast cancer, and loss of either paralog accelerated mammary tumorigenesis in mice. However, each paralog had a distinct impact on breast cancer. Thus, LATS2 depletion in luminal B tumors resulted in metabolic rewiring, with increased glycolysis and reduced peroxisome proliferator-activated receptor γ (PPARγ) signaling. Furthermore, pharmacological activation of PPARγ elicited LATS2-dependent death in luminal B-derived cells. In contrast, LATS1 depletion augmented cancer cell plasticity, skewing luminal B tumors towards increased expression of basal-like features, in association with increased resistance to hormone therapy. Hence, these two closely related paralogs play distinct roles in protection against breast cancer; tumors with reduced expression of either LATS1 or LATS2 may rewire signaling networks differently and thus respond differently to anticancer treatments.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center