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REP1 inhibits FOXO3-mediated apoptosis to promote cancer cell survival

Kwon-Ho Song1,2,3, Seon Rang Woo1,2,4, Joon-Yong Chung5

  • 1Laboratory of Tumor Immunology, Department of Biomedical Sciences, Graduate School of Medicine, Korea University, Seoul, Republic of Korea.

Cell Death & Disease
|January 6, 2017
PubMed

Insights

Rab escort protein 1 (REP1) is crucial for intestinal cell survival and colon cancer progression. Inhibiting REP1 enhances cancer cell apoptosis and retards tumor growth, suggesting REP1 as a therapeutic target.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Rab escort protein 1 (REP1) is a component of the Rab geranyl-geranyl transferase 2 complex.
  • Mutations in REP1 cause choroideremia (CHM), an X-linked eye disease.
  • REP1's role in normal and cancer cells beyond the eye is not fully understood.

Purpose of the Study:

  • To investigate the function of REP1 in intestinal cell survival and tumorigenesis.
  • To elucidate the molecular mechanisms of REP1-mediated cell survival.
  • To evaluate REP1 as a potential therapeutic target for colon cancer.

Main Methods:

  • Yeast two-hybrid (Y2H) assay to identify binding partners.
  • Cellular assays to assess apoptosis and nuclear translocation.
  • Xenograft tumor models to evaluate therapeutic efficacy.

Main Results:

  • REP1 is essential for intestinal cell survival and highly expressed in colon cancer.
  • Silencing REP1 sensitizes colon cancer cells to serum starvation and 5-FU-induced apoptosis.
  • REP1 interacts with FOXO3, inhibiting its nuclear translocation and suppressing FOXO3-mediated apoptosis.
  • Combined inhibition of REP1 and 5-FU significantly retarded tumor growth in vivo.

Conclusions:

  • REP1 plays a critical role in colon cancer cell survival and tumorigenesis.
  • REP1's interaction with FOXO3 is a key mechanism for its anti-apoptotic function.
  • REP1 represents a promising therapeutic target for combination treatment in colon cancer.

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