Overexpression of β1 integrin contributes to polarity reversal and a poor prognosis of breast invasive micropapillary carcinoma

© Liu et al. Invasive micropapillary carcinoma (IMPC) of the breast is a highly aggressive breast cancer. Polarity reversal exemplified by cluster growth is hypothesized to contribute to the invasiveness and metastasis of IMPC. In this study, we demonstrate that levels of β1 integrin and Rac1 expression were greater in breast IMPC than in invasive breast carcinoma of no specific type and paraneoplastic benign breast tissue. We show that silencing β1 integrin expression using the β1 integrin inhibitor AIIB2 partially restored polarity in IMPC primary cell clusters and downregulated Rac1. Thus, overexpression of β1 integrin upregulates Rac1. Univariate analysis showed that overexpression of β1 integrin and Rac1 was associated with breast cancer cell polarity reversal, lymph node metastasis, and poor disease-free survival in IMPC patients. Multivariate analysis revealed that polarity reversal was an independent predictor of poor disease-free survival. These findings indicate that overexpression of β1 integrin and the resultant upregulation of Rac1 contribute to polarity reversal and metastasis of breast IMPC, and that β1 integrin and Rac1 could be potential prognostic biomarkers and targets for treatment of breast IMPC

Optimizing medium for producing ethanol from industrial crop Jerusalem artichoke by one- step fermentation and recombinant Saccharomyces cerevisiae

In order to obtain a high ethanol yield from the Jerusalem artichoke raw extract and reduce the fermentation cost, we have engineered a new recombinant Saccharomyces cerevisiae strain that could produce ex-inulinase. The response surface methodology based on Plackett-Burman and Box-Behnken design was used to optimize the medium for the ethanol production from the Jerusalem artichoke raw extracts by the recombinant strain. In the first optimization step, Plackett-Burman design was employed to select significant factors, including concentrations of yeast extract, inoculum, and MgSO(4)7H(2)O. In the second step, the steepest ascent experiment was carried out to determine the center point with the three significant factors; the selected combinations were further optimized using the Box-Behnken design. The maximum ethanol production rate was predicted at 91.1g/l, which was based on a medium consisting of yeast extract 9.24g/l, inoculum 39.8ml/l, and MgSO(4)7H(2)O 0.45g/l. In the validating experiment, the ethanol fermentation rate reached 102.1g/l, closely matching the predicted rate.In order to obtain a high ethanol yield from the Jerusalem artichoke raw extract and reduce the fermentation cost, we have engineered a new recombinant Saccharomyces cerevisiae strain that could produce ex-inulinase. The response surface methodology based on Plackett-Burman and Box-Behnken design was used to optimize the medium for the ethanol production from the Jerusalem artichoke raw extracts by the recombinant strain. In the first optimization step, Plackett-Burman design was employed to select significant factors, including concentrations of yeast extract, inoculum, and MgSO(4)7H(2)O. In the second step, the steepest ascent experiment was carried out to determine the center point with the three significant factors; the selected combinations were further optimized using the Box-Behnken design. The maximum ethanol production rate was predicted at 91.1g/l, which was based on a medium consisting of yeast extract 9.24g/l, inoculum 39.8ml/l, and MgSO(4)7H(2)O 0.45g/l. In the validating experiment, the ethanol fermentation rate reached 102.1g/l, closely matching the predicted rate

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe