Unknown

Dataset Information

0

LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state.


ABSTRACT: 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 ? (PPAR?) signaling. Furthermore, pharmacological activation of PPAR? 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.

SUBMITTER: Furth N 

PROVIDER: S-EPMC6238411 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications


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,  ...[more]

Similar Datasets

2018-10-28 | GSE116818 | GEO
2018-10-28 | GSE116817 | GEO
2018-10-28 | GSE116816 | GEO
| PRJNA480288 | ENA
| PRJNA480289 | ENA
| PRJNA480291 | ENA
| S-EPMC6766663 | biostudies-literature
| S-EPMC6917744 | biostudies-literature
| S-EPMC7211035 | biostudies-literature
| S-EPMC7236108 | biostudies-literature