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.