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Effects of YAP1 and SFRP2 overexpression on the biological behavior of colorectal cancer cells and their molecular mechanisms

机译:YAP1和SFRP2过表达对结直肠癌细胞生物学行为的影响及其分子机制

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Background: Colorectal cancer (CRC) is one of the most common malignancies worldwide and has a high mortality rate. With the development of tumor molecular biology, more and more attention is being paid to the mechanisms of cell pathways in colorectal carcinogenesis, such as the Hippo/Yes-associated protein 1 (YAP1) and Wnt/β-catenin signaling pathways. The abnormal expression of YAP1 and β-catenin have been reported in CRC, and can lead to excessive cell proliferation, and eventually, tumor formation. Secreted frizzled-related protein 2 (SFRP2) levels have been found to be decreased in a variety of cancers, and SFRP2 is an antagonist that binds directly to Wnt signal. At present, the molecular basis of colorectal tumors is still not fully understood. In the present study, we sought to identify the molecular mechanisms underlying YAP1 and SFRP2 in the development of CRC. Methods: We constructed CRC cell lines that stably overexpressed YAP1 and SFRP2 using lentivirus packaging and cell infection. The levels of expression of the proteins were evaluated by western blot and immunofluorescence assays. Protein complex immunoprecipitation (Co-IP) was used to detect the interaction between YAP1, SFRP2, and β-catenin. The functional roles of YAP1 and SFRP2 in CRC was determined by a Cell Counting Kit-8 (CCK8) proliferation assay and flow cytometric apoptosis assay. Results: The data of the present study showed that the overexpression of SFRP2 promoted the expression of YAP1 and β-catenin protein, and the overexpression of YAP1 promoted the expression of β-catenin protein. YAP1 overexpression promoted cell proliferation, while SFRP2 overexpression inhibited cell proliferation and promoted cell apoptosis. Conclusions: Our findings showed that the expression of YAP1, SFRP2, and β-catenin is correlated in CRC cells. The Hippo pathway and Wnt pathway interact with each other in the pathogenesis of CRC, and YAP1 and SFRP2 are involved in the formation and development of CRC.
机译:背景:结直肠癌(CRC)是全球最常见的恶性肿瘤之一,并且死亡率高。随着肿瘤分子生物学的发展,越来越多地关注结肠直肠癌细胞途径的机制,例如河马/是相关蛋白1(YAP1)和Wnt /β-连环蛋白信号传导途径。 yap1和β-catenin的异常表达已在CRC中报告,可以导致细胞增殖过度,最终肿瘤形成。已经发现分泌的混浊相关的蛋白2(SFRP2)水平在各种癌症中降低,并且SFRP2是直接与WNT信号结合的拮抗剂。目前,结直肠肿瘤的分子基础仍未完全理解。在本研究中,我们试图在CRC的发育中鉴定YAP1和SFRP2基础的分子机制。方法:使用慢病毒包装和细胞感染构建稳定过表达YAP1和SAP1和SFRP2的CRC细胞系。通过蛋白质印迹和免疫荧光测定评估蛋白质的表达水平。使用蛋白质复合免疫沉淀(Co-IP)来检测YAP1,SFRP2和β-catenin之间的相互作用。 YAP1和SFRP2在CRC中的功能作用由细胞计数试剂盒-8(CCK8)增殖测定和流式细胞咬合细胞凋亡测定法测定。结果:本研究的数据表明,SFRP2的过表达促进了YAP1和β-连环蛋白蛋白的表达,并且YAP1的过表达促进了β-连环蛋白蛋白的表达。 YAP1过表达促进细胞增殖,而SFRP2过表达抑制细胞增殖和促进细胞凋亡。结论:我们的研究结果表明,YAP1,SFRP2和β-Catenin的表达在CRC细胞中相关。 Hippo途径和Wnt途径在CRC的发病机制中彼此相互作用,并且YAP1和SFRP2参与CRC的形成和开发。

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