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FAM46C/TENT5C functions as a tumor suppressor through inhibition of Plk4 activity

Karineh Kazazian1,2, Yosr Haffani3, Deanna Ng1

  • 1Lunenfeld Tanenbaum Research Institute, Sinai Health System, Toronto, ON, M5G 1X5, Canada.

Communications Biology
|August 19, 2020
PubMed

Insights

FAM46C suppresses cancer by inhibiting Polo-like kinase 4 (Plk4) activity, preventing centriole overduplication and metastasis. Loss of FAM46C in colorectal cancer correlates with advanced stages, identifying it as a potential tumor suppressor.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Polo-like kinase 4 (Plk4) is a serine/threonine kinase crucial for centriole duplication.
  • Elevated Plk4 expression in cancers leads to centriole overduplication, mitotic errors, and chromosomal instability.
  • Plk4 also influences cancer invasion and metastasis via actin cytoskeleton regulation.

Purpose of the Study:

  • To investigate the interaction between Plk4 and the protein FAM46C/TENT5C.
  • To determine FAM46C's role in regulating Plk4 activity and centriole duplication.
  • To assess FAM46C's potential as a tumor suppressor in cancer progression.

Main Methods:

  • Demonstrated physical interaction between Plk4 and FAM46C.
  • Assessed FAM46C localization to centrioles and its effect on Plk4 kinase activity.
  • Evaluated FAM46C's impact on cancer cell invasion and tumor growth in a xenograft model.
  • Analyzed FAM46C expression in patient-derived colorectal cancer tissues.

Main Results:

  • FAM46C interacts with Plk4, localizes to centrioles, and inhibits Plk4 kinase activity.
  • FAM46C suppresses Plk4-induced centriole overduplication independently of its nucleotidyl transferase activity.
  • FAM46C inhibits cancer cell invasion and suppresses tumor growth, counteracting Plk4's pro-cancer effects.
  • Loss of FAM46C expression is observed in colorectal tumors, worsening with advanced clinical stage.

Conclusions:

  • FAM46C acts as a tumor suppressor by inhibiting Plk4 activity.
  • FAM46C's function in suppressing Plk4-driven centriole duplication and cancer progression is clinically relevant.
  • Loss of FAM46C may contribute to cancer development and progression, particularly in colorectal cancer.

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