Deletion of 3p12-22 is frequent in multiple cancer types, indicating the presence of critical tumor-suppressor genes (TSGs) at this region. We studied a novel candidate TSG, CMTM7, located at the 3p22.3 CMTM-gene cluster, for its tumor-suppressive functions and related mechanisms. The three CMTM genes, CMTM6, 7 and 8, are broadly expressed in human normal adult tissues and normal epithelial cell lines. Only CMTM7 is frequently silenced or downregulated in esophageal and nasopharyngeal cell lines, but uncommon in other carcinoma cell lines. Immunostaining of tissue microarrays for CMTM7 protein showed its downregulation or absence in esophageal, gastric, pancreatic, liver, lung and cervix tumor tissues. Promoter CpG methylation and loss of heterozygosity were both found contributing to CMTM7 downregulation. Ectopic expression of CMTM7 in carcinoma cells inhibits cell proliferation, motility and tumor formation in nude mice, but not in immortalized normal cells, suggesting a tumor inhibitory role of CMTM7. The tumor-suppressive function of CMTM7 is associated with its role in G1/S cell cycle arrest, through upregulating p27 and downregulating cyclin-dependent kinase 2 (CDK2) and 6 (CDK6). Moreover, CMTM7 could promote epidermal growth factor receptor (EGFR) internalization, and further suppress AKT signaling pathway. Thus, our findings suggest that CMTM7 is a novel 3p22 tumor suppressor regulating G1/S transition and EGFR/AKT signaling during tumor pathogenesis.
We determined the historical change in soil organic carbon (SOC) stocks from long-term field trials that represent major soil types and climatic conditions of northern China. Soil carbon and general circulation models were validated using these field trial data sets. We then applied these models to predict future change in SOC stocks to 2100 using two net primary production (NPP) scenarios (i.e., current NPP or 1% year À1 NPP increase). The conversion rate of plant residues to SOC was higher in single-cropping sites than in double-cropping sites. The prediction of future SOC sequestration potential indicated that these soils will be a net source of carbon dioxide (CO 2 ) under no fertilizer inputs. Even when inorganic nutrients were applied, the additional carbon input from increased plant residues could not meet the depletion of SOC in parts of northern China. Manure or straw application could however improve the SOC sequestration potential at all sites. The SOC sequestration potential in northern China was estimated to be À4.3 to 18.2 t C ha À1 by 2100. The effect of projected climate change on the annual rate of SOC change did not differ significantly between climate scenarios. The average annual rate of SOC change under current and increased NPP scenarios (at 850 ppm CO 2 ) was approximately 0.136 t C ha À1 yr À1 in northern China. These findings highlight the need to maintain, and where possible increase, organic carbon inputs into these farming systems which are rapidly becoming inorganic fertilizer intensive.
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