Down-regulation of PINCH-1 Reduces Expression of EGFR, ERK1/2 and c-Myc, and Leads to Loss of Cell Viability in Colon Cancer Cells
Particularly interesting new cysteine-histidine rich protein (PINCH) is related to poor outcome in colorectal cancers. Here, the relationship between PINCH-1 and cell survival in colon cancer cells was analyzed and the signaling pathways regulated by PINCH-1 by using PINCH-1 siRNA. KM12C cells were treated with PINCH-1 siRNA or control siRNA. Cell number was analyzed by crystal violet staining and caspase-3 activity was assessed using a fluorescent substrate. PINCH-1 extra- and intracellular pathways in KM12C cells were investigated, using phospho-kinase/phospho-receptor tyrosine kinase (RTK) antibody arrays. The expression of c-Myc was evaluated by Quantitative real-time PCR (qPCR) and Western blot analysis. Cell number was significantly decreased (P=0.003) and the caspase-3 activity increased (P=0.019) in PINCH-1 depleted KM12C cultures compared to siRNA cultures. In PINCH-1 silenced KM12C cells, the levels of EGFR and ERK1/2 were significantly decreased (P=0.008, P=0.003, respectively) compared to their controls, as were the c-Myc mRNA and protein expressions (P=0.0073, P=0.0002, respectively). Down-regulation of PINCH-1 reduced the cell survival and lowers the levels of EGFR, ERK1/2 and c-Myc in colon cancer cells. PINCH-1 is essential for cell survival, and may be a future target for anticancer therapy.
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