Twist1-induced dissemination preserves epithelial identity and requires E-cadherin

Eliah R Shamir1, Elisa Pappalardo, Danielle M Jorgens

  • 1Department of Cell Biology and 2 Department of Oncology, Center for Cell Dynamics, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

Insights

Metastatic spread can occur without cells losing their epithelial identity. The study found that the transcription factor Twist1 can induce dissemination of epithelial cells, even with E-cadherin present.

Area of Science:

  • Cancer Biology
  • Cellular Biology
  • Molecular Oncology

Background:

  • Metastatic spread is a critical step in cancer progression.
  • Current models often link dissemination to the epithelial to mesenchymal transition (EMT), involving loss of E-cadherin and cell adhesion.
  • The precise molecular events initiating cell dissemination remain incompletely understood.

Purpose of the Study:

  • To identify the minimal molecular events required to induce dissemination of cells from primary murine mammary epithelium.
  • To investigate the role of E-cadherin and EMT transcription factors in initiating cell spread.

Main Methods:

  • Genetic manipulation of primary murine mammary epithelial cells.
  • Analysis of cell dissemination, epithelial architecture, and gene expression.
  • Investigated the role of E-cadherin and the EMT transcription factor Twist1.

Main Results:

  • E-cadherin deletion disrupted epithelial structure but rarely caused dissemination.
  • Expression of Twist1 induced rapid dissemination of epithelial cells.
  • Disseminating cells retained membrane-localized E-cadherin and β-catenin, and E-cadherin presence was crucial for Twist1-induced dissemination.

Conclusions:

  • Dissemination can occur in epithelial cells retaining their identity, without a full EMT.
  • Twist1 can trigger an epithelial motility program, facilitating spread.
  • These findings suggest alternative mechanisms for cancer cell metastasis that do not require a complete mesenchymal transition.

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