Identification of Y-Box Binding Protein 1 As a Core Regulator of MEK/ERK Pathway-Dependent Gene Signatures in Colorectal Cancer Cells

Transcriptional signatures are an indispensible source of correlative information on disease-related molecular alterations on a genome-wide level. Numerous candidate genes involved in disease and in factors of predictive, as well as of prognostic, value have been deduced from such molecular portraits, e.g. in cancer. However, mechanistic insights into the regulatory principles governing global transcriptional changes are lagging behind extensive compilations of deregulated genes. To identify regulators of transcriptome alterations, we used an integrated approach combining transcriptional profiling of colorectal cancer cell lines treated with inhibitors targeting the receptor tyrosine kinase (RTK)/RAS/mitogen-activated protein kinase pathway, computational prediction of regulatory elements in promoters of co-regulated genes, chromatin-based and functional cellular assays. We identified commonly co-regulated, proliferation-associated target genes that respond to the MAPK pathway. We recognized E2F and NFY transcription factor binding sites as prevalent motifs in those pathway-responsive genes and confirmed the predicted regulatory role of Y-box binding protein 1 (YBX1) by reporter gene, gel shift, and chromatin immunoprecipitation assays. We also validated the MAPK-dependent gene signature in colorectal cancers and provided evidence for the association of YBX1 with poor prognosis in colorectal cancer patients. This suggests that MEK/ERK-dependent, YBX1-regulated target genes are involved in executing malignant properties

Influence of temperature and relative humidity on survival and fecundity of three tsetse strains

International audienceBackground: Tsetse flies occur in much of sub-Saharan Africa where they are vectors of trypanosomes that cause human and animal African trypanosomosis. The sterile insect technique (SIT) is currently used to eliminate tsetse fly populations in an area-wide integrated pest management (AW-IPM) context in Senegal and Ethiopia. Three Glossina palpalis gambiensis strains [originating from Burkina Faso (BKF), Senegal (SEN) and an introgressed strain (SENbkf)] were established and are now available for use in future AW-IPM programmes against trypanosomes in West Africa. For each strain, knowledge of the environmental survival thresholds is essential to determine which of these strains is best suited to a particular environment or ecosystem, and can therefore be used effectively in SIT programmes. Methods: In this paper, we investigated the survival and fecundity of three G. p. gambiensis strains maintained under various conditions: 25 °C and 40, 50, 60, and 75 % relative humidity (rH), 30 °C and 60 % rH and 35 °C and 60 % rH. Results: The survival of the three strains was dependent on temperature only, and it was unaffected by changing humidity within the tested range. The BKF strain survived temperatures above its optimum better than the SEN strain. The SENbkf showed intermediate resistance to high temperatures. A temperature of about 32 °C was the limit for survival for all strains. A rH ranging from 40 to 76 % had no effect on fecundity at 25–26 °C. Conclusions: We discuss the implications of these results on tsetse SIT-based control programmes