Pathogenic BRCA1 variants disrupt PLK1-regulation of mitotic spindle orientation

Zhengcheng He; Ryan Ghorayeb; Susanna Tan; Ke Chen; Amanda C. Lorentzian; Jack Bottyan; Syed Mohammed Musheer Aalam; Miguel Angel Pujana; Philipp F. Lange; Nagarajan Kannan; Connie J. Eaves; Christopher A. Maxwell

doi:10.1038/s41467-022-29885-2

Nature Communications (Apr 2022)

Pathogenic BRCA1 variants disrupt PLK1-regulation of mitotic spindle orientation

Zhengcheng He,
Ryan Ghorayeb,
Susanna Tan,
Ke Chen,
Amanda C. Lorentzian,
Jack Bottyan,
Syed Mohammed Musheer Aalam,
Miguel Angel Pujana,
Philipp F. Lange,
Nagarajan Kannan,
Connie J. Eaves,
Christopher A. Maxwell

Affiliations

Zhengcheng He: Department of Pediatrics, University of British Columbia
Ryan Ghorayeb: Department of Pediatrics, University of British Columbia
Susanna Tan: Terry Fox Laboratory, British Columbia Cancer Research Institute
Ke Chen: Department of Pediatrics, University of British Columbia
Amanda C. Lorentzian: Department of Pediatrics, University of British Columbia
Jack Bottyan: Department of Pediatrics, University of British Columbia
Syed Mohammed Musheer Aalam: Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic
Miguel Angel Pujana: ProCURE, Catalan Institute of Oncology, Oncobell, Bellvitge Institute for Biomedical Research (IDIBELL), L’Hospitalet del Llobregat
Philipp F. Lange: Department of Pathology and Laboratory Medicine, University of British Columbia
Nagarajan Kannan: Division of Experimental Pathology and Laboratory Medicine, Department of Laboratory Medicine and Pathology, Mayo Clinic
Connie J. Eaves: Terry Fox Laboratory, British Columbia Cancer Research Institute
Christopher A. Maxwell: Department of Pediatrics, University of British Columbia

DOI: https://doi.org/10.1038/s41467-022-29885-2
Journal volume & issue: Vol. 13, no. 1
pp. 1 – 17

Abstract

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Female carriers of BRCA1 mutations possess high breast cancer risk, which may reflect deficient growth control of mammary progenitor cells. Here, the authors study progenitor-enriched fractions from these carriers and describe a loss of PLK1-mediated mitotic spindle positioning and an inability of the progeny to acquire features of mature luminal cells.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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