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Snail suppresses cellular senescence and promotes fibroblast-led cancer cell invasion

Satoshi Furuya1,2, Kaori Endo1, Akiko Takahashi3

  • 1Department of Biochemistry Interdisciplinary Graduate School of Medicine University of Yamanashi Japan.

FEBS Open Bio
|October 6, 2017
PubMed

Insights

Snail protein (SNAI1) regulates cell movement and senescence in cancer cells and fibroblasts. Suppressing Snail may offer a therapeutic strategy by reducing cancer cell invasion within the tumor microenvironment.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Snail (SNAI1) is a transcription factor known to induce epithelial-mesenchymal transition (EMT).
  • Fibroblasts play a crucial role in cancer progression, facilitating invasion through a process termed fibroblast-led cancer cell invasion.
  • The role of Snail in modulating cancer cell motility and its interaction with the tumor microenvironment requires further investigation.

Purpose of the Study:

  • To investigate the function of Snail (SNAI1) by examining the effects of its expression downregulation.
  • To determine the impact of Snail suppression on cellular senescence and motility in cancer cells and fibroblasts.
  • To elucidate the role of Snail in regulating fibroblast-led cancer cell invasion.

Main Methods:

  • Utilized short interfering RNA (siRNA) to suppress Snail expression in various cancer cell lines and normal IMR90 fibroblasts.
  • Assessed cellular senescence following Snail downregulation.
  • Evaluated cancer cell motility and the effects of coculturing Snail-silenced cancer cells with Snail-silenced IMR90 fibroblasts.

Main Results:

  • Suppression of Snail expression induced cellular senescence in multiple cancer cell types and in IMR90 fibroblasts.
  • Snail-silenced cancer cells demonstrated significantly reduced motility.
  • Cocultivation of Snail-silenced cancer cells with Snail-silenced IMR90 fibroblasts further decreased cancer cell motility, highlighting the role of Snail in both cell types for invasion.

Conclusions:

  • Snail regulates both cell motility and cellular senescence in cancer cells and fibroblasts.
  • These Snail-mediated functions in cancer cells and the surrounding microenvironment are critical modulators of fibroblast-led cancer cell invasion.
  • Targeting Snail expression locally in both cancer cells and the tumor microenvironment presents a promising therapeutic strategy against cancer progression.
Keywords:
EMTSnailcellular senescence

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