PrPC Regulates the Cancer Stem Cell Properties via Interaction With c-Met in Colorectal Cancer Cells

被引:10
作者
Lim, Ji ho [1 ,2 ]
Go, Gyeongyun [1 ,3 ]
Lee, Sang hun [1 ,2 ,3 ,4 ]
机构
[1] Soonchunhyang Univ, Coll Med, BK21FOUR Project 2, Dept Biochem, Cheonan, South Korea
[2] Soonchunhyang Univ, Seoul Hosp, Med Sci Res Inst, 59,Daesagwan Ro 657 Hannam Dong, Seoul 04401, South Korea
[3] Soonchunhyang Univ, Coll Med, Dept Biochem, Cheonan, South Korea
[4] Stembio Ltd, Entrepreneur 306, Asan, South Korea
基金
新加坡国家研究基金会;
关键词
c-Met; PrPC; colorectal cancer; crizotinib; cancer stem cell; PRION PROTEIN; OVEREXPRESSION; ACTIVATION; INHIBITOR; RECEPTOR;
D O I
10.21873/anticanres.15133
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:3459 / 3470
页数:12
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