LGALS3BP regulates centriole biogenesis and centrosome hypertrophy in cancer cells

Nat Commun. 2013;4:1531. doi: 10.1038/ncomms2517.

Abstract

Centrosome morphology and number are frequently deregulated in cancer cells. Here, to identify factors that are functionally relevant for centrosome abnormalities in cancer cells, we established a protein-interaction network around 23 centrosomal and cell-cycle regulatory proteins, selecting the interacting proteins that are deregulated in cancer for further studies. One of these components, LGALS3BP, is a centriole- and basal body-associated protein with a dual role, triggering centrosome hypertrophy when overexpressed and causing accumulation of centriolar substructures when downregulated. The cancer cell line SK-BR-3 that overexpresses LGALS3BP exhibits hypertrophic centrosomes, whereas in seminoma tissues with low expression of LGALS3BP, supernumerary centriole-like structures are present. Centrosome hypertrophy is reversed by depleting LGALS3BP in cells endogenously overexpressing this protein, supporting a direct role in centrosome aberration. We propose that LGALS3BP suppresses assembly of centriolar substructures, and when depleted, causes accumulation of centriolar complexes comprising CPAP, acetylated tubulin and centrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / metabolism*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line, Tumor
  • Centrioles / metabolism*
  • Centrioles / pathology*
  • Centrioles / ultrastructure
  • Chromatography, Affinity
  • Extracellular Matrix Proteins / metabolism
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • HEK293 Cells
  • Humans
  • Hypertrophy
  • Male
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Protein Interaction Maps
  • Protein Transport
  • Protein-Serine-Threonine Kinases / metabolism
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Seminoma / genetics
  • Seminoma / pathology
  • Spindle Apparatus / metabolism
  • Spindle Apparatus / ultrastructure

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Carrier Proteins
  • Extracellular Matrix Proteins
  • Glycoproteins
  • LGALS3BP protein, human
  • Lgals3bp protein, rat
  • RNA, Small Interfering
  • PLK4 protein, human
  • Protein-Serine-Threonine Kinases