RT Journal Article SR Electronic T1 LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201800171 DO 10.26508/lsa.201800171 VO 1 IS 5 A1 Furth, Noa A1 Pateras, Ioannis S A1 Rotkopf, Ron A1 Vlachou, Vassiliki A1 Rivkin, Irina A1 Schmitt, Ina A1 Bakaev, Deborah A1 Gershoni, Anat A1 Ainbinder, Elena A1 Leshkowitz, Dena A1 Johnson, Randy L A1 Gorgoulis, Vassilis G A1 Oren, Moshe A1 Aylon, Yael YR 2018 UL http://www.life-science-alliance.org/content/1/5/e201800171.abstract 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.