title: Rampant centrosome amplification underlies more aggressive disease course of triple negative breast cancers.
abstract: Centrosome amplification (CA), a cell-biological trait, characterizes pre-neoplastic and pre-invasive lesions and is associated with tumor aggressiveness. Recent studies suggest that CA leads to malignant transformation and promotes invasion in mammary epithelial cells. Triple negative breast cancer (TNBC), a histologically-aggressive subtype shows high recurrence, metastases, and mortality rates. Since TNBC and non-TNBC follow variable kinetics of metastatic progression, they constitute a novel test bed to explore if severity and nature of CA can distinguish them apart. We quantitatively assessed structural and numerical centrosomal aberrations for each patient sample in a large-cohort of grade-matched TNBC (n = 30) and non-TNBC (n = 98) cases employing multi-color confocal imaging. Our data establish differences in incidence and severity of CA between TNBC and non-TNBC cell lines and clinical specimens. We found strong correlation between CA and aggressiveness markers associated with metastasis in 20 pairs of grade-matched TNBC and non-TNBC specimens (p < 0.02). Time-lapse imaging of MDA-MB-231 cells harboring amplified centrosomes demonstrated enhanced migratory ability. Our study bridges a vital knowledge gap by pinpointing that CA underlies breast cancer aggressiveness. This previously unrecognized organellar inequality at the centrosome level may allow early-risk prediction and explain higher tumor aggressiveness and mortality rates in TNBC patients.
authors: Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors: Vaishali
authors: V
authors: Pannu
authors: Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors: Karuna
authors: K
authors: Mittal
authors: Department of Gynecologic Oncology, Northside Hospital Cancer Institute, Atlanta, GA 30342, USA.
authors: Guilherme
authors: G
authors: Cantuaria
authors: Department of Pathology, Emory University Hospital, Atlanta, GA 30322, USA.
authors: Michelle D
authors: MD
authors: Reid
authors: Department of Pathology, Emory University Hospital, Atlanta, GA 30322, USA.
authors: Xiaoxian
authors: X
authors: Li
authors: Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors: Shashikiran
authors: S
authors: Donthamsetty
authors: Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors: Michelle
authors: M
authors: McBride
authors: Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors: Sergey
authors: S
authors: Klimov
authors: Department of Mathematics and Statistics, Georgia State University, Atlanta, GA 30303, USA.|Neuroscience Institute, Georgia State University, Atlanta, GA 30303, USA.
authors: Remus
authors: R
authors: Osan
authors: Clinical Pathology & Anatomic Pathology, West Georgia Hospitals, LaGrange, GA 30240, USA.
authors: Meenakshi V
authors: MV
authors: Gupta
authors: Department of Biology, Georgia State University, Atlanta, GA 30303, USA.
authors: Padmashree C G
authors: PC
authors: Rida
authors: Department of Biology, Georgia State University, Atlanta, GA 30303, USA.|Institute of Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA.
authors: Ritu
authors: R
authors: Aneja
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D018385:Centrosome / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D015996:Survival Rate; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
keywords: centrosome amplification; disease prognosis; metastasis; triple negative breast cancer