Bladder cancer (BC) is very common and associated with significant morbidity and mortality, though the molecular underpinnings of its origination and progression remain poorly understood. In this study, we demonstrate that Prohibitin 1 (PHB) was overexpressed in human BC tissues and that PHB upregulation was associated with poor prognosis. We also found that PHB was necessary and sufficient for BC cell proliferation. Interestingly, the overexpressed PHB was primarily found within mitochondria, and we provide the first direct evidence that phosphorylation by Akt at Thr258 of PHB induces this mitochondrial localization. Inhibiton of Akt reverses these effects and inhibited the proliferation of BC cells. Finally, the phosphorylation of PHB was required for BC cell proliferation, further implicating the importance of the Akt in BC. Taken together, these findings identify the Akt/PHB signaling cascade as a novel mechanism of cancer cell proliferation and provide the scientific basis for the establishment of PHB as a new prognostic marker and treatment target for BC.

Background: Blocking vascular endothelial growth factor receptor (VEGFR) pathway can enhance the efficacy of EGFR-TKI in EGFRm NSCLC. ACTIVE is the first phase III study evaluating apatinib, an oral small molecule VEGFR2-TKI, or placebo plus gefitinib as first-line therapy in patients (pts) with EGFRm NSCLC.

No abstract

No abstract

Background: Education has been shown to be inversely associated with the incidence of lung cancer at several conventional observational studies. However, this association may be biased owing to the methodological limitations of traditional observational study-confounding, reverse causation, and measurement error. Therefore, we aimed to investigate whether more years spent in education is causally associated with risk of lung cancer through a two sample mendelian randomisation study. Methods: The main analysis used publicly available genetic summary data from two large consortiums (International Lung Cancer Consortium (ILCCO) and Social Science Genetic Association Consortium (SSGAC)). Genetic variants used as instrumental variables for lung cancer and years of education were derived from two large genome wide association studies: ILCCO and SSGAC, respectively. Finally, genetic data from three additional consortia (TAG, GLGC, GIANT) were analyzed to investigate whether longer education can causally alter the common lung cancer risk factors. The exposure was the genetic predisposition to higher levels of education, measured by 73 SNPs from SSGAC. The primary outcome was the risk of lung cancer (11348 events in ILCCO). Secondary outcomes based on different histologic subtypes were also examined.Results: Genetic predisposition towards 3.6 years of additional education was associated with a 52% lower risk of lung (odds ratio 0.48, 95% confidence interval 0.34 to 0.66; p ¼ 1.02 Â 10À5). Sensitivity analyses were consistent with a causal interpretation in which major bias from genetic pleiotropy was unlikely. The Mendelian randomisation assumptions did not seem to be violated. Genetic predisposition towards longer education was additionally associated with less smoking, lower body mass index, and a favorable blood lipid profile. Conclusions: Our present mendelian randomisation study provided strong evidence to support that higher education attainment plays a causal role in lowering the risk of lung cancer. Furthermore, more work is needed to elucidate the potential mechanisms which mediate the association between education and lung cancer.