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 Noa Furth
A1 Ioannis S Pateras
A1 Ron Rotkopf
A1 Vassiliki Vlachou
A1 Irina Rivkin
A1 Ina Schmitt
A1 Deborah Bakaev
A1 Anat Gershoni
A1 Elena Ainbinder
A1 Dena Leshkowitz
A1 Randy L Johnson
A1 Vassilis G Gorgoulis
A1 Moshe Oren
A1 Yael Aylon
YR 2018
UL https://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.