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Mesenchymal to Epithelial Transition Induced by Reprogramming Factors Attenuates the Malignancy of Cancer Cells

Mikiro Takaishi1, Masahito Tarutani1, Junji Takeda2

  • 1Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan.

Plos One
|June 4, 2016
PubMed

Insights

Reprogramming factors induce mesenchymal to epithelial transition (MET) in cancer cells, reducing their malignancy and metastasis. This MET process offers a potential new strategy for developing novel anticancer therapies targeting metastatic cancer.

Area of Science:

  • Oncology
  • Stem Cell Biology
  • Cancer Biology

Background:

  • Epithelial to mesenchymal transition (EMT) drives cancer metastasis, but effective therapies targeting this process are lacking.
  • Mesenchymal to epithelial transition (MET), the reverse of EMT, is observed in induced pluripotent stem cell generation.
  • Understanding MET in cancer could reveal new therapeutic strategies.

Purpose of the Study:

  • To investigate the effects of reprogramming factors (RFs) on squamous cell carcinoma (SCC) cells.
  • To determine if inducing MET in cancer cells can reduce their malignant potential.
  • To explore RFs as a potential therapeutic strategy against metastatic cancer.

Main Methods:

  • Introduction of reprogramming factors (RFs) into SCC cells to create RFs-introduced cancer cells (RICs).
  • Assessment of morphological and molecular changes (mRNA, microRNAs) in RICs.
  • In vitro evaluation of RICs' motility and invasive activities.
  • In vivo study using xenografts to assess lymph node metastasis in mice inoculated with RICs versus parental SCC cells.

Main Results:

  • RICs exhibited enhanced epithelial characteristics and altered gene/microRNA expression.
  • Motility and invasive activities of RICs were significantly reduced in vitro.
  • RIC xenografts showed no lymph node metastasis, unlike parental SCC xenografts.
  • RICs demonstrated a reversal of malignant phenotypes through MET.

Conclusions:

  • Inducing MET in SCC cells via RFs effectively reduces cancer cell malignancy and metastatic potential in vitro and in vivo.
  • The MET process in cancer cells, facilitated by RFs, represents a promising avenue for novel anticancer therapy development.
  • Targeting MET offers a potential strategy to combat metastatic cancer by reverting cells to a less aggressive epithelial state.

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