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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / metabolism*
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Line, Tumor
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Centrioles / metabolism*
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Centrioles / pathology*
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Centrioles / ultrastructure
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Chromatography, Affinity
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Extracellular Matrix Proteins / metabolism
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Gene Expression Regulation, Neoplastic
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Gene Knockdown Techniques
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Glycoproteins / genetics
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Glycoproteins / metabolism*
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HEK293 Cells
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Humans
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Hypertrophy
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Male
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Microtubules / metabolism
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Microtubules / ultrastructure
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Neoplasms / genetics
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Neoplasms / metabolism*
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Neoplasms / pathology*
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Protein Interaction Maps
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Protein Serine-Threonine Kinases / metabolism
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Protein Transport
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RNA, Small Interfering / metabolism
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Rats
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Rats, Sprague-Dawley
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Seminoma / genetics
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Seminoma / pathology
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Spindle Apparatus / metabolism
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Spindle Apparatus / ultrastructure
Substances
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Antigens, Neoplasm
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Biomarkers, Tumor
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Carrier Proteins
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Extracellular Matrix Proteins
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Glycoproteins
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LGALS3BP protein, human
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Lgals3bp protein, rat
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RNA, Small Interfering
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PLK4 protein, human
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Protein Serine-Threonine Kinases