Mutations in the WNT/beta-catenin pathway are responsible for initiating the majority of colorectal cancers (CRCs). We have previously shown that hyperactivation of this signaling by histone deacetylase inhibitors (HDACis) such as butyrate, a fermentation product of dietary fiber, promotes CRC cell apoptosis. The extent of association between beta-catenin and the transcriptional coactivator CREB-binding protein (CBP) influences WNT/catenin signaling and, therefore, colonic cell physiology. CBP functions as a histone acetylase (HAT); therefore, we hypothesized that the modulation of WNT/catenin activity by CBP modifies the ability of the HDACi butyrate to hyperinduce WNT signaling and apoptosis in CRC cells. Our findings indicate that CBP affects the hyperinduction of WNT activity by butyrate. ICG-001, which specifically blocks association between CBP and beta-catenin, abrogates the butyrate-triggered increase in the number of CRC cells with high levels of WNT/catenin signaling. Combination treatment of CRC cells with ICG-001 and butyrate results in cell type-specific effects on apoptosis. Further, both butyrate and ICG-001 repress CRC cell proliferation, with additive effects in suppressing cell growth. Our study strongly suggests that ICG-001-like agents would be effective against butyrate/HDACi-resistant CRC cells. Therefore, ICG-001-like agents may represent an important therapeutic option for CRCs that exhibit low-fold hyperactivation of WNT activity and apoptosis in the presence of HDACis. The findings generated from this study may lead to approaches that utilize modulation of CBP activity to facilitate CRC therapeutic or chemopreventive strategies.

It is well documented that earnings inequalities have risen in many high-income countries. Less clear are the linkages between rising income inequality and workplace dynamics, how within- and between-workplace inequality varies across countries, and to what extent these inequalities are moderated by national labor market institutions. In order to describe changes in the initial between- and within-firm market income distribution we analyze administrative records for 2,000,000,000+ job years nested within 50,000,000+ workplace years for 14 high-income countries in North America, Scandinavia, Continental and Eastern Europe, the Middle East, and East Asia. We find that countries vary a great deal in their levels and trends in earnings inequality but that the between-workplace share of wage inequality is growing in almost all countries examined and is in no country declining. We also find that earnings inequalities and the share of between-workplace inequalities are lower and grew less strongly in countries with stronger institutional employment protections and rose faster when these labor market protections weakened. Our findings suggest that firm-level restructuring and increasing wage inequalities between workplaces are more central contributors to rising income inequality than previously recognized.

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Extant research on the gender pay gap suggests that men and women who do the same work for the same employer receive similar pay, so that processes sorting people into jobs are thought to account for the vast majority of the pay gap. Data that can identify women and men who do the same work for the same employer are rare, and research informing this crucial aspect of gender differences in pay is several decades old and from a limited number of countries. Here, using recent linked employer–employee data from 15 countries, we show that the processes sorting people into different jobs account for substantially less of the gender pay differences than was previously believed and that within-job pay differences remain consequential.