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 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.
ABSTRACT
The present study examined the processing of unit fractions and the extent to which it is affected by context. Using a numerical comparison task we found evidence for a holistic representation of unit fractions when the immediate context of the fractions was emphasized, that is when the stimuli set included in addition to the unit fractions also the numbers 0 and 1. The holistic representation was indicated by the semantic congruity effect for comparisons of pairs of fractions and by the distance effect in comparisons of a fraction and 0 and 1. Consistent with previous results (Bonato, Fabbri, Umilta, & Zorzi, 2007) there was no evidence for a holistic representation of unit fractions when the stimulus set included only fractions. These findings suggest that fraction processing is context-dependent. Finally, the present results are discussed in the context of processing other complex numbers beyond the first decade.
