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

M Dahlmann, A Okhrimenko, P Marcinkowski… - Oncotarget, 2014 - ncbi.nlm.nih.gov
M Dahlmann, A Okhrimenko, P Marcinkowski, M Osterland, P Herrmann, J Smith…
Oncotarget, 2014ncbi.nlm.nih.gov
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 …
Abstract
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).
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