Role of mTORC1 in intestinal epithelial repair and tumorigenesis

Harleen Kaur, Régis Moreau

Research output: Contribution to journalReview article

1 Scopus citations

Abstract

Abstract: mTORC1 signaling is the prototypical pathway regulating protein synthesis and cell proliferation. mTORC1 is active in stem cells located at the base of intestinal crypts but silenced as transit-amplifying cells differentiate into enterocytes or secretory cells along the epithelium. After an insult or injury, self-limiting and controlled activation of mTORC1 is critical for the renewal and repair of intestinal epithelium. mTORC1 promotes epithelial cell renewal by driving cryptic stem cell division, and epithelial cell repair by supporting the dedifferentiation and proliferation of enterocytes or secretory cells. Under repeated insult or injury, mTORC1 becomes constitutively active, triggering an irreversible return to stemness, cell division, proliferation, and inflammation among dedifferentiated epithelial cells. Epithelium-derived cytokines promulgate inflammation within the lamina propria, which in turn releases inflammatory factors that act back on the epithelium where undamaged intestinal epithelial cells participate in the pervading state of inflammation and become susceptible to tumorigenesis. Graphical abstract: [Figure not available: see fulltext.].

Original languageEnglish (US)
JournalCellular and Molecular Life Sciences
DOIs
StatePublished - Jan 1 2019

Keywords

  • Cell proliferation
  • Colorectal cancer
  • Immunity
  • Pro-inflammatory cytokines
  • Stem cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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