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Oct4 通过激活 SCF/c-Kit 信号通路促进结肠癌细胞的增殖、迁移、侵袭和上皮-间充质转化(EMT)。

Oct4 promoted proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in colon cancer cells by activating the SCF/c-Kit signaling pathway.

机构信息

Department of Cancer Center, Third Hospital of Shanxi Medical University, Taiyuan, China.

Department of Medical Laboratory, Shanxi Bethune Hospital, Taiyuan, China.

出版信息

Cell Cycle. 2023 Feb;22(3):291-302. doi: 10.1080/15384101.2022.2112486. Epub 2022 Oct 18.

Abstract

Octamer-binding transcription factor 4 (Oct4) is closely related to the occurrence and development of cancer. In the present study, we paid a special interest in exploring the effect of Oct4 on colon cancer (CC) proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) and its molecular mechanism. Immunohistochemistry (IHC) was used to detect the expression level of Oct4 in colon tissue of patients with colon cancer. Oct4 overexpression vector pcDNA-Oct4 was used to stably express Oct4 in human colon cancer cells HT29 and SW480. Cell counting kit-8 (CCK-8) assay was used to detect the cell proliferation. The invasion and migration abilities were observed by transwell and wound healing assays. The expression of EMT relate genes were observed by Western blot. We found that Oct4 was up-regulated in human colon cancer tissues than that in paracancerous tissues. The proliferation, migration, and invasion of HT29 and SW480 cells was significantly induced by transfection of pcDNA-Oct4. Furthermore, Oct4 overexpression enhanced EMT of CC cells, characterized by the increased expression of vimentin, Twist, and Snail, as well as decreased expression of E-cadherin. Mechanistically, Oct4 overexpression activated stem cell factor (SCF)/c-Kit signaling pathway in CC cells, and the SCF/c-Kit signaling inhibitor imatinib reversed pro-oncogenic effects of Oct4. These finding provide an insight into the potential of Oct4 for CC diagnosis and therapy.

摘要

八聚体结合转录因子 4(Oct4)与癌症的发生和发展密切相关。在本研究中,我们特别关注探讨 Oct4 对结肠癌(CC)增殖、迁移、侵袭和上皮间质转化(EMT)的影响及其分子机制。免疫组织化学(IHC)检测结肠癌患者结肠组织中 Oct4 的表达水平。使用 Oct4 过表达载体 pcDNA-Oct4 稳定表达人结肠癌 HT29 和 SW480 细胞中的 Oct4。细胞计数试剂盒(CCK-8)检测细胞增殖。通过 Transwell 和划痕愈合实验观察细胞侵袭和迁移能力。Western blot 观察 EMT 相关基因的表达。我们发现 Oct4 在人结肠癌组织中的表达高于癌旁组织。pcDNA-Oct4 的转染显著诱导 HT29 和 SW480 细胞的增殖、迁移和侵袭。此外,Oct4 的过表达增强了 CC 细胞的 EMT,表现为波形蛋白、Twist 和 Snail 的表达增加,以及 E-钙黏蛋白的表达减少。机制上,Oct4 的过表达激活了 CC 细胞中的干细胞因子(SCF)/c-Kit 信号通路,而 SCF/c-Kit 信号通路抑制剂伊马替尼逆转了 Oct4 的致癌作用。这些发现为 Oct4 用于 CC 的诊断和治疗提供了新的思路。

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