Selective phosphatidylinositol 3 kinase (PI3K) inhibitors are being actively tested in clinical trials for ER alpha-positive (ER +) breast cancer due to the presence of activating PIK3CA mutations. However, recent stu...
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Selective phosphatidylinositol 3 kinase (PI3K) inhibitors are being actively tested in clinical trials for ER alpha-positive (ER +) breast cancer due to the presence of activating PIK3CA mutations. However, recent studies have revealed that increased ER alpha transcriptional activity limits the efficacy of PI3K inhibitor monotherapy for ER + breast cancers. Herein, we report the identification of BTF3 as an oncogenic transcription factor that regulates ER alpha expression in luminal breast cancers. Our TCGA analysis reveals high expression levels of BTF3 in luminal/ER + breast cancer and cell line models harboring ERa overexpression. Concordantly, BTF3 expression is highly and strongly associated with ESR1 expression in multiple breast cancer cohorts. We further show that BTF3 promotes the proliferation, survival and migration of ER + breast cancer cells by modulating ESR1 expression and ER alpha-dependent transcription. Moreover, BTF3 knockdown sensitizes ER + breast cancer cells to the PI3K alpha inhibitor BYL-719 in both in vitro and in vivo models. Together, our findings highlight a novel role of BTF3 in modulation of ER alpha-dependent transcriptional activity and its potential as a predictive marker for the response to PI3K-targeted therapy in ER + breast cancer.
Microplastics（MPs） are important exempla of the Anthropocene and are exerting an increasing impact on Earth's carbon cycle. The huge imbalance between the MPs floating on the marine surface and those that are es...
Microplastics（MPs） are important exempla of the Anthropocene and are exerting an increasing impact on Earth's carbon cycle. The huge imbalance between the MPs floating on the marine surface and those that are estimated to have been introduced into the ocean necessitates a detailed assessment of marine MP sinks. Here, we demonstrate that cold seep sediments, which are characterized by methane fluid seepage and a chemosynthetic ecosystem, effectively capture and accommodate small-scale（< 100 μm） MPs, with 16 types of MPs being detected. The abundance of MPs in the surface of the sediment is higher in methane-seepage locations than in non-seepage areas. Methane seepage is beneficial to the accumulation, fragmentation, increased diversity, and aging of MPs. In turn, the rough surfaces of MPs contribute to the sequestration of the electron acceptor ferric oxide, which is associated with the anaerobic oxidation of methane（AOM）. The efficiency of the AOM determines whether the seeping methane（which has a greenhouse effect 83 times greater than that of CO2over a 20-year period） can enter the atmosphere,which is important to the global methane cycle, since the deep-sea environment is regarded as the largest methane reservoir associated with natural gas hydrates.
Carnivorous members of the Carnivora reside at the apex of food chains and consume meat-only diets, rich in purine, fats and protein. Here, we aimed to identify potential adaptive evolutionary signatures compatible wi...
Carnivorous members of the Carnivora reside at the apex of food chains and consume meat-only diets, rich in purine, fats and protein. Here, we aimed to identify potential adaptive evolutionary signatures compatible with high purine and fat metabolism based on analysis of host genomes and symbiotic gut microbial metagenomes. We found that the gut microbiomes of carnivorous Carnivora (e.g., Felidae, Canidae) clustered in the same Glade, and other clades comprised omnivorous and herbivorous Carnivora (e.g., badgers, bears and pandas). The relative proportions of genes encoding enzymes involved in uric acid degradation were higher in the gut microbiomes of meat-eating carnivorans than plant-eating species. Adaptive amino acid substitutions in two enzymes, carnitine O-palmitoyltransferase 1 (CPT1A) and lipase F (LIPF), which play a role in fat digestion, were identified in Felidae-Candidae species. Carnivorous carnivorans appear to endure diets high in purines and fats via gut microbiomic and genomic adaptations.
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