LGALS3BP regulates centriole biogenesis and centrosome hypertrophy in cancer cells

Marie-Laure Fogeron; Hannah Müller; Sophia Schade; Felix Dreher; Verena Lehmann; Anne Kühnel; Anne-Kathrin Scholz; Karl Kashofer; Alexandra Zerck; Beatrix Fauler; Rudi Lurz; Ralf Herwig; Kurt Zatloukal; Hans Lehrach; Johan Gobom; Eckhard Nordhoff; Bodo M H Lange

doi:10.1038/ncomms2517

LGALS3BP regulates centriole biogenesis and centrosome hypertrophy in cancer cells

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

Authors

Marie-Laure Fogeron¹, Hannah Müller, Sophia Schade, Felix Dreher, Verena Lehmann, Anne Kühnel, Anne-Kathrin Scholz, Karl Kashofer, Alexandra Zerck, Beatrix Fauler, Rudi Lurz, Ralf Herwig, Kurt Zatloukal, Hans Lehrach, Johan Gobom, Eckhard Nordhoff, Bodo M H Lange

Affiliation

¹ Department of Vertebrate Genomics, Max-Planck Institute for Molecular Genetics, 14195 Berlin, Germany.

PMID: 23443559
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 Serine-Threonine Kinases / metabolism
Protein Transport
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