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

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.

Keywords: Colon cancer; Oct4; SCF/c-Kit signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colonic Neoplasms* / genetics
  • Epithelial-Mesenchymal Transition* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Signal Transduction

Substances

  • POU5F1 protein, human

Grants and funding

This study was supported by a grant from the Shanxi Science and Technology Department, key research and development project [Project No. 201903D321027].