7 research outputs found
RESCUE OF HIPPO CO-ACTIVATOR YAP1 TRIGGERS DNA DAMAGE-INDUCED APOPTOSIS IN HEMATOLOGICAL CANCERS
Oncogene–induced DNA damage elicits genomic instability in epithelial cancer cells, but apoptosis is blocked through inactivation of the tumor suppressor p53. In hematological cancers, the relevance of ongoing DNA damage and mechanisms by which apoptosis is suppressed are largely unknown. We found pervasive DNA damage in hematologic malignancies including multiple myeloma, lymphoma and leukemia, which leads to activation of a p53–independent, pro-apoptotic network centered on nuclear relocalization of ABL1 kinase. Although nuclear ABL1 triggers cell death through its interaction with the Hippo pathway co–activator YAP1 in normal cells, we show that low YAP1 levels prevent nuclear ABL1–induced apoptosis in these hematologic malignancies. YAP1 is under the control of a serine–threonine kinase, STK4. Importantly, genetic inactivation of STK4 restores YAP1 levels, triggering cell death in vitro and in vivo. Our data therefore identify a novel synthetic–lethal strategy to selectively target cancer cells presenting with endogenous DNA damage and low YAP1 levels
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Higher amounts of sedentary time are associated with short sleep duration and poor sleep quality in postmenopausal women
To evaluate the associations between sedentary time, total (total-PA), light (light-PA), moderate (MOD-PA), and vigorous (VIG-PA) physical activity with indices of sleep in postmenopausal women.
Baseline self-reported data from the Women's Health Initiative Observational Study (n = 75 074) were used in this cross-sectional analysis. Total-PA, light-PA, MOD-PA, and VIG-PA were categorized by metabolic equivalents of the activity (MET-hour [hr]/week [wk]) and were estimated using validated questionnaires. Sedentary time was categorized by hr/day and was estimated via questionnaire. Logistic regression was used to examine the associations between these variables and short sleep (≤6 hr/night), long sleep (≥10 hr/night), poor sleep quality, and insomnia symptoms after adjustment for age, race, socioeconomic status, body mass index, health status, depressive symptoms, smoking status, alcohol use, hormone therapy, and comorbidities.
Higher sedentary time (>11 hr/day) was associated with higher odds of short sleep (odds ratio [OR] = 1.80, 95% confidence interval [CI]: 1.72-1.88), poor sleep quality (OR = 1.85, 95% CI: 1.74-1.97), and insomnia symptoms (OR = 1.56, 95% CI: 1.49-1.64). Light-PA (>0 MET-hr/wk) was associated with lower odds of short sleep (OR = 0.96, 95% CI: 0.92-1.00), and higher amounts of total-PA (OR = 0.90, 95% CI: 0.84-0.97), light-PA (OR = 0.94, 95% CI: 0.89-1.00), and MOD-PA (OR = 0.91, 95% CI: 0.86-0.97) were associated with lower odds of poor sleep quality.
Our findings suggest that higher levels of light and moderate intensity physical activity are associated with better sleep quality, whereas higher amounts of sedentary time are associated with short sleep and lower quality sleep. Future studies should investigate the directionality of these associations and potential causal pathways