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PrPC 调节结直肠癌细胞中与 c-Met 的相互作用,从而影响癌症干细胞特性。

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

机构信息

Department of Biochemistry, BK21FOUR Project2, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.

Medical Science Research Institute, Soonchunhyang University Seoul Hospital, Seoul, Republic of Korea.

出版信息

Anticancer Res. 2021 Jul;41(7):3459-3470. doi: 10.21873/anticanres.15133.

Abstract

BACKGROUND/AIM: Studies have reported that the expression of c-Met and PrP improves tumor progression. However, not much is known about their relationship. We hypothesized that c-Met and PrP 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 PrP 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 PrP in CRC cells compared to normal colon epithelial cells. We revealed that the c-Met and PrP 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 PrP interact with each other, and targeting c-Met using crizotinib could be a powerful strategy for CRC therapy.

摘要

背景/目的:研究报道 c-Met 和 PrP 的表达可促进肿瘤进展。然而,它们之间的关系尚不清楚。我们假设 c-Met 和 PrP 相互作用,增强癌症干细胞(CSC)的特征。

材料与方法

采用磁激活细胞分选检测 c-Met 和 PrP 之间的相互作用,研究这种相互作用对下游信号、干细胞标志物表达和结直肠癌细胞(CRC)球体形成的影响。

结果

与正常结肠上皮细胞相比,CRC 细胞中 c-Met 和 PrP 的表达和结合水平增加。我们揭示 c-Met 和 PrP 的相互作用诱导 ERK 激活和 Oct4 的上调。克唑替尼抑制 c-Met 可减少 ERK 激活和 Oct4 表达,并抑制 CSC 特性。

结论

c-Met 和 PrP 相互作用,使用克唑替尼靶向 c-Met 可能是 CRC 治疗的有效策略。

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