BackgroundFocal adhesion plays an essential role in tumour invasiveness and metastasis. Hippo component YAP has been widely reported to be involved in many aspects of tumour biology. However, its role in focal adhesion regulation in breast cancer remains unexplored.MethodsTissue microarray was used to evaluate YAP expression in clinical breast cancer specimens by immunohistochemical staining. Cell migration and invasion abilities were measured by Transwell assay. A cell adhesion assay was used to measure the ability of cell adhesion to gelatin. The focal adhesion was visualized through immunofluorescence. Phosphorylated FAK and other proteins were detected by Western blot analysis. Gene expression profiling was used to screen differently expressed genes, and gene ontology enrichment was performed using DAVID software. The gene mRNA levels were measured by quantitative real-time PCR. The activity of the THBS1-promoter was evaluated by dual luciferase assay. Chromatin immunoprecipitation (ChIP) was used to verify whether YAP could bind to the THBS1-promoter region. The prediction of potential protein-interaction was performed with the String program. The ChIP sequence data of TEAD was obtained from the ENCODE database and analysed via the ChIP-seek tool. The gene expression dataset (GSE30480) of purified tumour cells from primary breast tumour tissues and metastatic lymph nodes was used in the gene set enrichment analysis. Prognostic analysis of the TCGA dataset was performed by the SurvExpress program. Gene expression correlation of the TCGA dataset was analysed via R2: Genomics Analysis and Visualization Platform.ResultsOur study provides evidence that YAP acts as a promoter of focal adhesion and tumour invasiveness via regulating FAK phosphorylation in breast cancer. Further experiments reveal that YAP could induce FAK phosphorylation through a TEAD-dependent manner. Using gene expression profiling and bioinformatics analysis, we identify the FAK upstream gene, thrombospondin 1, as a direct transcriptional target of YAP-TEAD. Silencing THBS1 could reverse the YAP-induced FAK activation and focal adhesion.ConclusionOur results unveil a new signal axis, YAP/THBS1/FAK, in the modulation of cell adhesion and invasiveness, and provides new insights into the crosstalk between Hippo signalling and focal adhesion.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0850-z) contains supplementary material, which is available to authorized users.
An activatable nanoprobe for imaging breast cancer metastases through near infrared‐I (NIR‐I)/NIR‐II fluorescence imaging and multispectral optoacoustic tomography (MSOT) imaging was designed. With a dihydroxanthene moiety serving as the electron donor, quinolinium as the electron acceptor and nitrobenzyloxydiphenylamino as the recognition element, the probe can specifically respond to nitroreductase and transform into an activated D‐π‐A structure with a NIR emission band extending beyond 900 nm. The activated nanoprobe exhibits NIR emission enhanced by aggregation‐induced emission (AIE) and produces strong optoacoustic signal. The nanoprobe was used to detect and image metastases from the orthotopic breast tumors to lymph nodes and then to lung in two breast cancer mouse models. Moreover, the nanoprobe can monitor the treatment efficacy during chemotherapeutic course through fluorescence and MSOT imaging.
Universal health coverage (UHC) is driving the global health agenda. Many countries have embarked on national policy reforms towards this goal, including China. In 2009, the Chinese government launched a new round of healthcare reform towards UHC, aiming to provide universal coverage of basic healthcare by the end of 2020. The year of 2019 marks the 10th anniversary of China’s most recent healthcare reform. Sharing China’s experience is especially timely for other countries pursuing reforms to achieve UHC. This study describes the social, economic and health context in China, and then reviews the overall progress of healthcare reform (1949 to present), with a focus on the most recent (2009) round of healthcare reform. The study comprehensively analyses key reform initiatives and major achievements according to four aspects: health insurance system, drug supply and security system, medical service system and public health service system. Lessons learnt from China may have important implications for other nations, including continued political support, increased health financing and a strong primary healthcare system as basis.
Universal health coverage (UHC) has been identified as a priority for the global health agenda. In 2009, the Chinese government launched a new round of healthcare reform towards UHC, aiming to provide universal coverage of basic healthcare by the end of 2020. We conducted a secondary data analysis and combined it with a literature review, analysing the overview of UHC in China with regard to financial protection, coverage of health services and the reported coverage of the WHO and the World Bank UHC indicators. The results include the following: out-of-pocket expenditures as a percentage of current health expenditures in China have dropped dramatically from 60.13% in 2000 to 35.91% in 2016; the health insurance coverage of the total population jumped from 22.1% in 2003 to 95.1% in 2013; the average life expectancy increased from 72.0 to 76.4, maternal mortality dropped from 59 to 29 per 100 000 live births, the under-5 mortality rate dropped from 36.8 to 9.3 per 1000 live births, and neonatal mortality dropped from 21.4 to 4.7 per 1000 live births between 2000 and 2017; and so on. Our findings show that while China appears to be well on the path to UHC, there are identifiable gaps in service quality and a requirement for ongoing strengthening of financial protections. Some of the key challenges remain to be faced, such as the fragmented and inequitable health delivery system, and the increasing demand for high-quality and value-based service delivery. Given that China has committed to achieving UHC and ‘Healthy China 2030’, the evidence from this study can be suggestive of furthering on in the UHC journey and taking the policy steps necessary to secure change.
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