Contribution of Different Carbon Sources to Isoprene Biosynthesis in Poplar Leaves

This study was performed to test if alternative carbon sources besides recently photosynthetically fixed CO(2) are used for isoprene formation in the leaves of young poplar (Populus × canescens) trees. In a (13)CO(2) atmosphere under steady state conditions, only about 75% of isoprene became (13)C labeled within minutes. A considerable part of the unlabeled carbon may be derived from xylem transported carbohydrates, as may be shown by feeding leaves with [U-(13)C]Glc. As a consequence of this treatment approximately 8% to 10% of the carbon emitted as isoprene was (13)C labeled. In order to identify further carbon sources, poplar leaves were depleted of leaf internal carbon pools and the carbon pools were refilled with (13)C labeled carbon by exposure to (13)CO(2). Results from this treatment showed that about 30% of isoprene carbon became (13)C labeled, clearly suggesting that, in addition to xylem transported carbon and CO(2), leaf internal carbon pools, e.g. starch, are used for isoprene formation. This use was even increased when net assimilation was reduced, for example by abscisic acid application. The data provide clear evidence of a dynamic exchange of carbon between different cellular precursors for isoprene biosynthesis, and an increasing importance of these alternative carbon pools under conditions of limited photosynthesis. Feeding [1,2-(13)C]Glc and [3-(13)C]Glc to leaves via the xylem suggested that alternative carbon sources are probably derived from cytosolic pyruvate/phosphoenolpyruvate equivalents and incorporated into isoprene according to the predicted cleavage of the 3-C position of pyruvate during the initial step of the plastidic deoxyxylulose-5-phosphate pathway

RAGE mediates S100A4-induced cell motility via MAPK/ERK and hypoxia signaling and is a prognostic biomarker for human colorectal cancer metastasis

Survival of colorectal cancer patients is strongly dependent on development of distant metastases. S100A4 is a prognostic biomarker and inducer for colorectal cancer metastasis. Besides exerting intracellular functions, S100A4 is secreted extracellularly. The receptor for advanced glycation end products (RAGE) is one of its interaction partners. The impact of the S100A4-RAGE interaction for cell motility and metastasis formation in colorectal cancer has not been elucidated so far. Here we demonstrate the RAGE-dependent increase in migratory and invasive capabilities of colorectal cancer cells via binding to extracellular S100A4. We show the direct interaction of S100A4 and RAGE, leading to hyperactivated MAPK/ERK and hypoxia signaling. The S100A4-RAGE axis increased cell migration (P<0.005) and invasion (P<0.005), which was counteracted with recombinant soluble RAGE and RAGE-specific antibodies. In colorectal cancer patients, not distantly metastasized at surgery, high RAGE expression in primary tumors correlated with metachronous metastasis, reduced overall (P=0.022) and metastasis-free survival (P=0.021). In summary, interaction of S100A4-RAGE mediates S100A4-induced colorectal cancer cell motility. RAGE by itself represents a biomarker for prognosis of colorectal cancer. Thus, therapeutic approaches targeting RAGE or intervening in S100A4-RAGE-dependent signaling early in tumor progression might represent alternative strategies restricting S100A4-induced colorectal cancer metastasis