The Rb tumor suppressor regulates epithelial cell migration and polarity

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Tiziana Parisi1, Michele Balsamo1, Frank Gertler1,2

  • 1The David H. Koch Institute for Integrative Cancer Research, Cambridge, Massachusetts.

Molecular Carcinogenesis
|August 8, 2018
PubMed

Insights

Inactivating the retinoblastoma (Rb) tumor suppressor impairs epithelial cell migration and tissue repair by disrupting cell polarity. Loss of Rb and p53 together promotes cancer metastasis through distinct mechanisms.

Area of Science:

  • Oncology
  • Cell Biology
  • Cancer Research

Background:

  • Altered cell polarity and migration are critical features of cancer and metastasis.
  • The retinoblastoma (Rb) tumor suppressor plays a known role in regulating cell proliferation.

Purpose of the Study:

  • To investigate the role of Rb inactivation in epithelial cell migration and tissue closure.
  • To elucidate the mechanisms by which Rb and p53 mutations cooperate in cancer development.

Main Methods:

  • Analysis of Rb null epithelial cells and their migratory and polarization capabilities.
  • Assessment of RhoA signaling pathways and apical-basal polarity protein localization.
  • Evaluation of the effects of concomitant tp53 inactivation on Rb null cell behavior.

Main Results:

  • Rb inactivation leads to defects in tissue closure, characterized by impaired epithelial cell migration and polarization.
  • These defects are independent of Rb's anti-proliferative function and linked to RhoA signaling upregulation and polarity protein mislocalization.
  • Concomitant inactivation of tp53 rescues the motility defect but not the aberrant polarity in Rb null cells.

Conclusions:

  • Rb inactivation critically affects cell migration and polarity, contributing to cancer progression.
  • Rb and p53 mutations cooperate through distinct pathways to promote cancer development and metastasis.
  • Targeting these pathways may offer new therapeutic strategies for metastatic cancers.
Keywords:
PAR complexRhoA Rock signalingaPKCeyes open phenotypeplanar cell polarity

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