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Endocr Relat Cancer. 2017 Sep;24(9):T47-T64. doi: 10.1530/ERC-17-0072. Epub 2017 May 17.

Centrosome amplification: a suspect in breast cancer and racial disparities.

Author information

1
Department of BiologyGeorgia State University, Atlanta, Georgia, USA.
2
Department of BiologyGeorgia State University, Atlanta, Georgia, USA raneja@gsu.edu.

Abstract

The multifaceted involvement of centrosome amplification (CA) in tumorigenesis is coming into focus following years of meticulous experimentation, which have elucidated the powerful abilities of CA to promote cellular invasion, disrupt stem cell division, drive chromosomal instability (CIN) and perturb tissue architecture, activities that can accelerate tumor progression. Integration of the extant in vitro, in vivo and clinical data suggests that in some tissues CA may be a tumor-initiating event, in others a consequential 'hit' in multistep tumorigenesis, and in some others, non-tumorigenic. However, in vivo data are limited and primarily focus on PLK4 (which has CA-independent mechanisms by which it promotes aggressive cellular phenotypes). In vitro breast cancer models suggest that CA can promote tumorigenesis in breast cancer cells in the setting of p53 loss or mutation, which can both trigger CA and promote cellular tolerance to its tendency to slow proliferation and induce aneuploidy. It is thus our perspective that CA is likely an early hit in multistep breast tumorigenesis that may sometimes be lost to preserve aggressive karyotypes acquired through centrosome clustering-mediated CIN, both numerical and structural. We also envision that the robust link between p53 and CA may underlie, to a considerable degree, racial health disparity in breast cancer outcomes. This question is clinically significant because, if it is true, then analysis of centrosomal profiles and administration of centrosome declustering drugs could prove highly efficacious in risk stratifying breast cancers and treating African American (AA) women with breast cancer.

KEYWORDS:

breast; carcinoma

PMID:
28515047
PMCID:
PMC5837860
DOI:
10.1530/ERC-17-0072
[Indexed for MEDLINE]
Free PMC Article

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