RIP140 Represses Intestinal Paneth Cell Differentiation and Interplays with SOX9 Signaling in Colorectal Cancer

Antoine Gleizes1, Mouna Triki1, Sandrine Bonnet1

  • 1IRCM-Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, Université de Montpellier, Institut Régional du Cancer de Montpellier, CNRS, 208 rue des Apothicaires, F-34298 Montpellier, France.

Cancers
|July 2, 2021
PubMed

Insights

RIP140 represses Paneth cell differentiation by inhibiting SOX9 expression and activity. This RIP140-SOX9 cross-talk impacts gut homeostasis and colorectal cancer progression.

Area of Science:

  • Molecular Biology
  • Gastroenterology
  • Oncology

Background:

  • RIP140 is a key regulator of gut homeostasis and tumorigenesis via Wnt/APC signaling.
  • Paneth cells are crucial for intestinal epithelium integrity and function.
  • The interplay between RIP140 and SOX9 in Paneth cell differentiation is not well understood.

Purpose of the Study:

  • To investigate the role of RIP140 in Paneth cell differentiation.
  • To elucidate the interaction between RIP140 and the transcription factor SOX9.
  • To determine the clinical significance of RIP140 and SOX9 in colorectal cancer.

Main Methods:

  • Loss-of-function mouse models and human colon cancer cells were utilized.
  • Gene expression and protein interactions were analyzed using RT-qPCR, immunohistochemistry, and GST-pull down assays.
  • Transcriptional activity was assessed via luciferase reporter assays.

Main Results:

  • RIP140 was found to repress Paneth cell lineage by inhibiting SOX9 expression.
  • RIP140 directly interacts with SOX9, suppressing its transcriptional activity.
  • The Wnt signaling pathway differentially regulates SOX9 and RIP140.
  • RIP140 and SOX9 expression levels show an inverse correlation and prognostic value in colorectal cancer.

Conclusions:

  • RIP140 acts as a repressor of Paneth cell differentiation through SOX9 inhibition.
  • A significant cross-talk exists between RIP140 and SOX9 in intestinal pathophysiology.
  • The RIP140-SOX9 axis represents a potential therapeutic target for colorectal cancer.

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