CEP135 isoform dysregulation promotes centrosome amplification in breast cancer cells

Molecular Biology of the Cell
Divya Ganapathi SankaranChad G Pearson

Abstract

The centrosome, composed of two centrioles surrounded by pericentriolar material, is the cell's central microtubule-organizing center. Centrosome duplication is coupled with the cell cycle such that centrosomes duplicate once in S phase. Loss of such coupling produces supernumerary centrosomes, a condition called centrosome amplification (CA). CA promotes cell invasion and chromosome instability, two hallmarks of cancer. We examined the contribution of centriole overduplication to CA and the consequences for genomic stability in breast cancer cells. CEP135, a centriole assembly protein, is dysregulated in some breast cancers. We previously identified a short isoform of CEP135, CEP135mini, that represses centriole duplication. Here, we show that the relative level of full-length CEP135 (CEP135full) to CEP135mini (the CEP135full:mini ratio) is increased in breast cancer cell lines with high CA. Inducing expression of CEP135full in breast cancer cells increases the frequency of CA, multipolar spindles, anaphase-lagging chromosomes, and micronuclei. Conversely, inducing expression of CEP135mini reduces centrosome number. The differential expression of the CEP135 isoforms in vivo is generated by alternative polyadenylation. Directed...Continue Reading

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Citations

Dec 25, 2019·The Journal of Cell Biology·Elizabeth M ParkAndrew J Holland
Mar 4, 2020·International Journal of Molecular Sciences·Xiaokun ZhouDan Xu
Aug 28, 2019·International Journal of Molecular Sciences·Lorenza González-MariscalChristian Hernández-Guzmán
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Methods Mentioned

BETA
reverse transcription PCR
PCR
transfection
fluorescence imaging

Software Mentioned

Nikon NIS Elements
tiff
NumPy
READS
Python

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