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Area of Science:

  • Cell Biology
  • Cancer Research
  • Biophysics

Background:

  • Epithelial-to-mesenchymal transition (EMT) and collagen fibril maturation in the tumor microenvironment are key drivers of cancer invasion and metastasis.
  • Cell migration is enhanced by confinement along fiber-like tracks, but the combined effect of EMT and such tracks on migration is not well understood.

Purpose of the Study:

  • To investigate how TGFβ-mediated EMT influences cancer cell migration on collagen fiber-like tracks.
  • To explore the role of Golgi positioning regulation in EMT-enhanced cell migration and persistence.

Main Methods:

  • Utilized micropatterned collagen tracks to mimic the tumor microenvironment.
  • Quantified cell migration speed and persistence in response to TGFβ-induced EMT.
  • Analyzed Golgi positioning dynamics and stability in relation to cell migration parameters.

Main Results:

  • EMT doubled migration speed and tripled persistence on fiber-like tracks compared to untreated cells.
  • EMT induced a rearward bias in Golgi positioning but stabilization of Golgi position was a stronger predictor of migration enhancement.
  • Golgi stability, not just position, significantly correlated with variations in cell migration speed.

Conclusions:

  • Cell-intrinsic EMT and extrinsic fibrillar tracks have non-redundant, synergistic effects on cancer cell motility.
  • Golgi positioning stability, potentially acting as a physical scaffold, is crucial for efficient force distribution and sustained cell migration.
  • Understanding Golgi dynamics in EMT could reveal new therapeutic targets for inhibiting cancer metastasis.