Single-copy Snail upregulation causes partial epithelial-mesenchymal transition in colon cancer cells

BMC Cancer. 2023 Feb 14;23(1):153. doi: 10.1186/s12885-023-10581-3.

Abstract

Background: Epithelial-mesenchymal transition (EMT) is an embryonic programme implicated in cancer stem cells, metastasis and therapeutic resistance. Its role in cancer progression remains controversial because the transition can be partial or complete in different models and contexts.

Methods: Using human colon cancer DLD-1 cells, we engineered a cell line with a single-copy of Snail that was doxycycline-inducible and compared it to existing EMT models in DLD-1. The effect of Snail upregulation was characterised functionally, morphologically, and by transcriptional profiling and protein expression.

Results: Induction with doxycycline increased Snail expression to a level similar to that observed in cancer cell lines spontaneously expressing Snail and results in partial EMT. In comparison, higher levels of overexpression arising from introduction of episomal-Snail, results in complete EMT. DLD-1 cells with partial EMT show chemoresistance in vitro, increased tumour growth in vivo and decreased apoptosis.

Conclusions: These findings highlight that the amount of bioavailable Snail can dictate phenotypic outcome and that partial EMT may be a preferred outcome of models operating within a natural range of Snail overexpression.

Keywords: Epithelial-mesenchymal transition; Metastasis; Partial transition; SNAIL.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement
  • Colonic Neoplasms* / genetics
  • Colonic Neoplasms* / metabolism
  • Doxycycline / pharmacology
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Snail Family Transcription Factors* / genetics
  • Snail Family Transcription Factors* / metabolism
  • Up-Regulation

Substances

  • Doxycycline
  • Snail Family Transcription Factors
  • SNAI1 protein, human