Aberrant Expression and Subcellular Localization of ECT2 Drives Colorectal Cancer Progression and Growth

ECT2 is an activator of RHO GTPases that is essential for cytokinesis. In addition, ECT2 was identified as an oncoprotein when expressed ectopically in NIH/3T3 fibroblasts. However, oncogenic activation of ECT2 resulted from N-terminal truncation, and such truncated ECT2 proteins have not been found in patients with cancer. In this study, we observed elevated expression of fulllength ECT2 protein in preneoplastic colon adenomas, driven by increased ECT2mRNAabundance and associated with APC tumorsuppressor loss. Elevated ECT2 levels were detected in the cytoplasm and nucleus of colorectal cancer tissue, suggesting cytoplasmic mislocalization as one mechanism of early oncogenic ECT2 activation. Importantly, elevated nuclear ECT2 correlated with poorly differentiated tumors, and a low cytoplasmic:nuclear ratio of ECT2 protein correlated with poor patient survival, suggesting that nuclear and cytoplasmic ECT2 play distinct roles in colorectal cancer. Depletion of ECT2 reduced anchorage-independent cancer cell growth and invasion independent of its function in cytokinesis, and loss of Ect2 extended survival in a KrasG12D Apc-null colon cancer mouse model. Expression of ECT2 variants with impaired nuclear localization or guanine nucleotide exchange catalytic activity failed to restore cancer cell growth or invasion, indicating that active, nuclear ECT2 is required to support tumor progression. Nuclear ECT2 promoted ribosomal DNA transcription and ribosome biogenesis in colorectal cancer. These results support a driver role for both cytoplasmic and nuclear ECT2 overexpression in colorectal cancer and emphasize the critical role of precise subcellular localization in dictating ECT2 function in neoplastic cells

VOC emissions and carbon balance of two bioenergy plantations in response to nitrogen fertilization: A comparison of Miscanthus and Salix.

Energy crops are an important renewable source for energy production in future. To ensure high yields of crops, N fertilization is a common practice. However, knowledge on environmental impacts of bioenergy plantations, particularly in systems involving trees, and the effects of N fertilization is scarce. We studied the emission of volatile organic compounds (VOC), which negatively affect the environment by contributing to tropospheric ozone and aerosols formation, from Miscanthus and willow plantations. Particularly, we aimed at quantifying the effect of N fertilization on VOC emission. For this purpose, we determined plant traits, photosynthetic gas exchange and VOC emission rates of the two systems as affected by N fertilization (0 and 80 kg hayr). Additionally, we used a modelling approach to simulate (i) the annual VOC emission rates as well as (ii) the OHreactivity resulting from individual VOC emitted. Total VOC emissions from Salix was 1.5- and 2.5-fold higher compared to Miscanthus in non-fertilized and fertilized plantations, respectively. Isoprene was the dominating VOC in Salix (80-130 μg gDW h), whereas it was negligible in Miscanthus. We identified twenty-eight VOC compounds, which were released by Miscanthus with the green leaf volatile hexanal as well as dimethyl benzene, dihydrofuranone, phenol, and decanal as the dominant volatiles. The pattern of VOC released from this species clearly differed to the pattern emitted by Salix. OHreactivity from VOC released by Salix was ca. 8-times higher than that of Miscanthus. N fertilization enhanced stand level VOC emissions, mainly by promoting the leaf area index and only marginally by enhancing the basal emission capacity of leaves. Considering the higher productivity of fertilized Miscanthus compared to Salix together with the considerably lower OHreactivity per weight unit of biomass produced, qualified the C-perennial grass Miscanthus as a superior source of future bioenergy production