Krüppel-Like Factor 8 Is a New Wnt/Beta-Catenin Signaling Target Gene and Regulator in Hepatocellular Carcinoma

Krüppel-like factor 8 (KLF8) plays important role in cell cycle and oncogenic transformation. Here we report the mechanisms by which KLF8 crosstalks with Wnt/β-catenin signaling pathway and regulates hepatocellular carcinoma (HCC) cells proliferation. We show that overexpression of KLF8 and nucleus accumulation of β-catenin in the human HCC samples are positively correlated. More importantly, KLF8 protein levels plus nucleus accumulation of β-catenin levels were significantly elevated in high-grade HCC compared to low-grade HCC. Using HCC HepG2 cells we find that, on the one hand both protein and mRNA of KLF8 are up-regulated under Wnt3a stimulation, on the other hand overexpression of KLF8 increases the cytoplasm and nucleus accumulation of β-catenin, recruits p300 to β-catenin/T-cell factor 4 (TCF4) transcription complex, enhances TOP flash report gene transcription, and induces Wnt/β-catenin signaling target genes c-Myc, cyclin D1 and Axin1 expression. Knockdown of KLF8 using shRNA inhibits Wnt3a induced transcription of TOP flash report gene and expression of c-Myc, cyclin D1 and Axin1. Knockdown of β-catenin by shRNA rescues the enhanced HepG2 and Hep3B cells proliferation ability induced by overexpression of KLF8

Climate, soil organic layer, and nitrogen jointly drive forest development after fire in the North American boreal zone

Previous empirical work has shown that feedbacks between fire severity, soil organic layer thickness, tree recruitment, and forest growth are important factors controlling carbon accumulation after fire disturbance. However, current boreal forest models inadequately simulate this feedback. We address this deficiency by updating the ED2 model to include a dynamic feedback between soil organic layer thickness, tree recruitment, and forest growth. The model is validated against observations spanning monthly to centennial time scales and ranging from Alaska to Quebec. We then quantify differences in forest development after fire disturbance resulting from changes in soil organic layer accumulation, temperature, nitrogen availability, and atmospheric CO2. First, we find that ED2 accurately reproduces observations when a dynamic soil organic layer is included. Second, simulations indicate that the presence of a thick soil organic layer after a mild fire disturbance decreases decomposition and productivity. The combination of the biological and physical effects increases or decreases total ecosystem carbon depending on local conditions. Third, with a 48C temperature increase, some forests transition from undergoing succession to needleleaf forests to recruiting multiple cohorts of broadleaf trees, decreasing total ecosystem carbon by �40% after 300 years. However, the presence of a thick soil organic layer due to a persistently mild fire regime can prevent this transition and mediate carbon losses even under warmer temperatures. Fourth, nitrogen availability regulates successional dynamics; broadleaf species are less competitive with needleleaf trees under low nitrogen regimes. Fifth, the boreal forest shows additional short-term capacity for carbon sequestration as atmospheric CO2 increases