TY - JOUR T1 - LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201800171 VL - 1 IS - 5 SP - e201800171 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 Y1 - 2018/10/01 UR - https://www.life-science-alliance.org/content/1/5/e201800171.abstract N2 - 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. ER -