FAM46C/TENT5C Functions As a Tumor Suppressor Through Inhibition of Plk4 Activity

Overview

Journal Commun Biol

Specialty Biology

Date 2020 Aug 19

PMID 32807875

Citations 15

Authors

Karineh Kazazian

Yosr Haffani

Deanna Ng

Chae Min Michelle Lee

Wendy Johnston

Minji Kim

Roland Xu

Karina Pacholzyk

Francis Si-Wah Zih

Julie Tan

Alannah Smrke

Aaron Pollett

Hannah Sun-Tsi Wu

Carol Jane Swallow

Affiliations

Soon will be listed here.

Abstract

Polo like kinase 4 (Plk4) is a tightly regulated serine threonine kinase that governs centriole duplication. Increased Plk4 expression, which is a feature of many common human cancers, causes centriole overduplication, mitotic irregularities, and chromosomal instability. Plk4 can also promote cancer invasion and metastasis through regulation of the actin cytoskeleton. Herein we demonstrate physical interaction of Plk4 with FAM46C/TENT5C, a conserved protein of unknown function until recently. FAM46C localizes to centrioles, inhibits Plk4 kinase activity, and suppresses Plk4-induced centriole duplication. Interference with Plk4 function by FAM46C was independent of the latter's nucleotidyl transferase activity. In addition, FAM46C restrained cancer cell invasion and suppressed MDA MB-435 cancer growth in a xenograft model, opposing the effect of Plk4. We demonstrate loss of FAM46C in patient-derived colorectal cancer tumor tissue that becomes more profound with advanced clinical stage. These results implicate FAM46C as a tumor suppressor that acts by inhibiting Plk4 activity.

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