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BRMS1: a multifunctional signaling molecule in metastasis

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Abstract

Despite high mortality rates, molecular understanding of metastasis remains limited. It can be regulated by both pro- and anti-metastasis genes. The metastasis suppressor, breast cancer metastasis suppressor 1 (BRMS1), has been positively correlated with patient outcomes, but molecular functions are still being characterized. BRMS1 has been implicated in focal adhesion kinase (FAK), epidermal growth factor receptor (EGFR), and NF-κB signaling pathways. We review evidence that BRMS1 regulates these vast signaling pathways through chromatin remodeling as a member of mSin3 histone deacetylase complexes.

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Abbreviations

AA:

Amino acid

BRMS1:

Breast cancer metastasis suppressor 1

cAMP:

Cyclic AMP

CDK2:

Cyclin-dependent kinase 2

CK2α:

Casein kinase 2 alpha

CoREST:

Co-repressor of REST

CTC:

Circulating tumor cells

Cx26:

Connexin 26

Cx43:

Connexin 43

ECM:

Extracellular microenvironment

EGF:

Epidermal growth factor

EGFR:

Epidermal growth factor receptor

EMT:

Epithelial-to-mesenchymal transition

FAK:

Focal adhesion kinase

FGF:

Fibroblast growth factor

GFs:

Growth factors

GIJC:

Gap junction intercellular communication

GO:

Gene Ontology

HCC:

Hepatocellular carcinoma

HDAC1:

Histone deacetylase 1

HDAC2:

Histone deacetylase 2

MHC:

Major histocompatibility complex

miRNA:

microRNA

MMP:

Matrix metalloproteinases

mSin3:

Mammalian switch-independent 3

nCOR:

Nuclear receptor corepressor

NLS:

Nuclear localization signal

NSCLC:

Non-small cell lung cancer

NuRD:

Nucleosome remodeling and deacetylase

OPN:

Osteopontin

PKA:

Protein kinase A

PtdIns(4,5)P2 :

Phosphatidylinositol 4,5-bisphosphate

ROS:

Reactive oxygen species

TGFα:

Transforming growth factor alpha

TGF-β:

Transforming growth factor beta

TME:

Tumor microenvironment

uPA:

Urokinase plasminogen activator

UTR:

Untranslated region

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Funding

Work done in the authors’ lab was funded primarily by Susan G. Komen for the Cure (SAC110037), METAvivor Research and Support, Inc., the National Foundation for Cancer Research; and USPHS-National Institutes of Health grants (CA87728; CA134981). Additional funding support was provided by National Cancer Institute P30-CA168524 (DRW) and National Institutes of Health GM103418 (DRW). We apologize to any authors whose work was omitted due to article guidelines. We also thank Christa Manton, Michael Washburn, Thuc Ly, Adam Scheid, and Thomas Beadnell for helpful discussions, careful reading, and editing of this manuscript.

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  1. Department of Cancer Biology, The Kansas University Medical Center, 3901 Rainbow Blvd., Kansas City, KS, 66160, USA

    Rosalyn C. Zimmermann & Danny R. Welch

  2. The University of Kansas Cancer Center, 3901 Rainbow Blvd, Kansas City, KS, 66160, USA

    Danny R. Welch

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  1. Rosalyn C. Zimmermann
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Correspondence to Danny R. Welch.

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Zimmermann, R.C., Welch, D.R. BRMS1: a multifunctional signaling molecule in metastasis. Cancer Metastasis Rev 39, 755–768 (2020). https://doi.org/10.1007/s10555-020-09871-0

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