Τίτλος:
LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2018 Furth et al.
Συγγραφείς:
Furth, N.
Pateras, I.S.
Rotkopf, R.
Vlachou, V.
Rivkin, I.
Schmitt, I.
Bakaev, D.
Gershoni, A.
Ainbinder, E.
Leshkowitz, D.
Johnson, R.L.
Gorgoulis, V.G.
Oren, M.
Aylon, Y.
Περιοδικό:
Life Science Alliance
Εκδότης:
Rockefeller University Press
DOI:
10.26508/lsa.201800171
