RIP140 regulates transcription factor HES1 oscillatory expression and mitogenic activity in colon cancer cells

Nour Sfeir1,2,3,4, Marilyn Kajdan1,2,3,4, Stéphan Jalaguier1,2,3,4

  • 1IRCM, Institut de Recherche en Cancérologie de Montpellier, France.

Molecular Oncology
|March 9, 2024
PubMed

Insights

Receptor-interacting protein 140 (RIP140) influences colorectal cancer by regulating the Notch/HES1 pathway. It impacts HES1 expression and colon cancer cell proliferation, affecting patient survival.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • Receptor-interacting protein 140 (RIP140) is known to regulate intestinal homeostasis and tumorigenesis via Wnt signaling.
  • The Notch signaling pathway plays a critical role in various cellular processes, including cancer development.

Purpose of the Study:

  • To investigate the role of RIP140 in the Notch/HES1 signaling pathway.
  • To elucidate the mechanism by which RIP140 affects HES1 gene expression and colorectal cancer (CRC) cell proliferation.

Main Methods:

  • In vitro studies using CRC cell lines to assess RIP140's effect on HES1 gene expression.
  • Analysis of RIP140 and HES1 expression correlation in mouse intestine and human CRC samples.
  • Investigation of RIP140's interaction with HES1 and its impact on mitogenic activity and patient survival.

Main Results:

  • RIP140 positively regulates HES1 gene expression transcriptionally through a RBPJ/NICD-mediated mechanism in CRC cells.
  • RIP140 and HES1 expression are significantly correlated in mouse and human CRC tissues.
  • RIP140 directly interacts with HES1, inhibiting its mitogenic activity and influencing patient survival in CRC.
  • RIP140 exhibits a dual effect on HES1 transcription, inhibiting it when the Notch pathway is highly activated.

Conclusions:

  • RIP140 is a key regulator of the Notch/HES1 signaling pathway in colorectal cancer.
  • RIP140 modulates HES1 gene expression and colon cancer cell proliferation, impacting patient outcomes.

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