No abstract

Malignant mesothelioma is a locally aggressive and highly lethal neoplasm. Dysregulation and activation of Gas6/AXL tyrosine kinase signaling are associated with mesothelioma progression, but the mechanisms of these AXL tumorigenic roles are poorly understood. p53 mutants in lung carcinoma upregulate AXL expression by binding and acetylating the AXL promoter. Although TP53 mutations are uncommon in mesothelioma, we hypothesized that these tumors might have alternative feedback mechanisms between AXL and p53. In the current report, we investigated AXL regulation of TP53 transcription, expression, and biological function in mesothelioma. AXL expression was stronger in mesothelioma than most of the other tumor types from the TCGA gene expression profile dataset. AXL knockdown by shRNA induced wild-type and mutant p53 expression in mesothelioma cell lines, suggesting that AXL pro-tumorigenic roles result in part from the suppression of p53 function. Likewise, induced AXL inhibited expression of wild type p53 in COS-7 cells and 293T cells. Immunofluorescence staining showed nuclear colocalization of AXL and p53; however, association of AXL and p53 was not demonstrated in immunoprecipitation complexes. The AXL effects on p53 expression resulted from the inhibition of TP53 transcription, as demonstrated by qRT-PCR after AXL silencing and TP53 promotor dual luciferase activity assays. Chromatin immunoprecipitation-qPCR and sequencing showed that AXL bound to the initial 600 bp sequence at the 5′ end of the TP53 promoter. AXL inhibition (shRNA or R428) reduced mesothelioma cell viability, migration, and invasion, whereas TP53 shRNA knockdown attenuated antiproliferative, migration, and invasive effects of AXL silencing or AXL inactivation in these cells. These studies demonstrate a novel feedback regulation loop between AXL and p53, and provide a rationale for mesothelioma therapies targeting AXL/p53 signaling.

No abstract

No abstract

Quantitative identification of the location of cultural and creative industries has always been an important issue in the study of micro-locations in human geography. However, most of the previous studies on the location of cultural and creative industries focused on the macro description of the existing cultural and creative industry and lacked quantitative identification of micro-locations suitable for cultivating and developing cultural and creative industries. Therefore, based on the relevant location theory of cultural and creative industries, the urban creative field strength and its quantitative model are proposed. From the perspective of the built environment, 500 m × 500 m grids were established as analysis units based on multi-source data, including society, economy and geography data, using the geographic information system (GIS) analysis technology and spatial entropy weight overlay method to describe and visualize the micro-locations of urban cultural and creative industries. Based on the empirical study in Hangzhou, the following can be concluded: (1) the study method of “single index measurement–entropy method weighting–space weighted summation–hot spot analysis” constructed can quantitatively identify the micro-location of urban cultural and creative industries. It proves that the research framework proposed is scientifically valid. (2) The overall field strength of the creative field in Hangzhou has a circular structure with multiple centers, gradually decreasing outward from the main urban area of Hangzhou, with the sub-centers of the creative field scattered around the core urban area. The most suitable location for the cultivation and development of cultural and creative industries in Hangzhou is located in Wensan District as the core area, which includes Wensan Road, Xueyuan Road, Wulin Square, Hangzhou Future City-Xixi Wetland, etc. (3) The location around the provincial/city/district government land is the core area of creative field strength, which is more suitable for the development of cultural and creative industries. The farther from the core area, the smaller the creative field strength is, and the more obvious the attenuation of distance is.