PT  - JOURNAL ARTICLE
AU  - Noa Furth
AU  - Ioannis S Pateras
AU  - Ron Rotkopf
AU  - Vassiliki Vlachou
AU  - Irina Rivkin
AU  - Ina Schmitt
AU  - Deborah Bakaev
AU  - Anat Gershoni
AU  - Elena Ainbinder
AU  - Dena Leshkowitz
AU  - Randy L Johnson
AU  - Vassilis G Gorgoulis
AU  - Moshe Oren
AU  - Yael Aylon
TI  - LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state
AID  - 10.26508/lsa.201800171
DP  - 2018 Oct 01
TA  - Life Science Alliance
PG  - e201800171
VI  - 1
IP  - 5
4099  - https://www.life-science-alliance.org/content/1/5/e201800171.short
4100  - https://www.life-science-alliance.org/content/1/5/e201800171.full
SO  - Life Sci. Alliance2018 Oct 01; 1
AB  - 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.