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Inhibiting β-catenin disables nucleolar functions in triple-negative breast cancer. Cell Death Dis 2021 Mar 04;12(3):242

Date

03/06/2021

Pubmed ID

33664239

Pubmed Central ID

PMC7933177

DOI

10.1038/s41419-021-03531-z

Scopus ID

2-s2.0-85102032030   6 Citations

Abstract

Triple-negative breast cancer (TNBC) patients with upregulated Wnt/β-catenin signaling often have poor clinical prognoses. During pathological examinations of breast cancer sections stained for β-catenin, we made the serendipitous observation that relative to non-TNBC, specimens from TNBC patients have a greater abundance of nucleoli. There was a remarkable direct relationship between nuclear β-catenin and greater numbers of nucleoli in TNBC tissues. These surprising observations spurred our investigations to decipher the differential functional relevance of the nucleolus in TNBC versus non-TNBC cells. Comparative nucleolar proteomics revealed that the majority of the nucleolar proteins in TNBC cells were potential targets of β-catenin signaling. Next, we undertook an analysis of the nucleolar proteome in TNBC cells in response to β-catenin inhibition. This effort revealed that a vital component of pre-rRNA processing, LAS1 like ribosome biogenesis factor (LAS1L) was significantly decreased in the nucleoli of β-catenin inhibited TNBC cells. Here we demonstrate that LAS1L protein expression is significantly elevated in TNBC patients, and it functionally is important for mammary tumor growth in xenograft models and enables invasive attributes. Our observations highlight a novel function for β-catenin in orchestrating nucleolar activity in TNBCs.

Author List

Weeks SE, Kammerud SC, Metge BJ, AlSheikh HA, Schneider DA, Chen D, Wei S, Mobley JA, Ojesina AI, Shevde LA, Samant RS

Author

Akinyemi Ojesina MD, PhD Assistant Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Nucleolus
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
MCF-7 Cells
Mice, Inbred NOD
Mice, SCID
Nuclear Proteins
Proteome
Proteomics
Triple Negative Breast Neoplasms
Tumor Burden
Wnt Signaling Pathway
beta Catenin