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PrPC Regulates the Cancer Stem Cell Properties via Interaction With c-Met in Colorectal Cancer Cells
Ji Ho Lim1,2, Gyeongyun Go1,3, Sang Hun Lee4,2,3,5
1Department of Biochemistry, BK21FOUR Project2, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.
Background/Aim:
Studies have reported that the expression of c-Met and PrPC improves tumor progression. However, not much is known about their relationship. We hypothesized that c-Met and PrPC interact with each other, and enhance cancer stem cell (CSC) characteristics.
Materials And Methods:
Magnetic activated cell sorting was used to examine the interaction between c-Met and PrPC The effects of the interaction on downstream signals, stem cell marker expression, and sphere formation of colorectal cancer (CRC) cells were investigated.
Results:
We demonstrated the increased expression and binding levels of c-Met and PrPC in CRC cells compared to normal colon epithelial cells. We revealed that the c-Met and PrPC interaction induced the ERK activation and Oct4 upregulation. The inhibition of c-Met by crizotinib reduced ERK activation and Oct4 expression and suppressed CSC properties.
Conclusion:
c-Met and PrPC interact with each other, and targeting c-Met using crizotinib could be a powerful strategy for CRC therapy.
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