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Trends in Stem Cell Proliferation and Cancer Research pp 251–275Cite as

Signaling Pathways of MTA Family Proteins as Regulators of Cancer Progression and Metastasis

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Abstract

The metastasis-associated (MTA) gene family is a family of cancer-progression-related genes and their encoded products. The expression of MTA1 messenger RNA or MTA1 protein has been repeatedly reported to correlate with various malignant properties, including prognosis in a wide range of human cancers. MTA proteins are involved in the nucleosome remodeling and histone deacetylation complex and function as transcriptional corepressors. In addition, tumor suppressor protein p53 is deacetylated and inactivated by both MTA1 and MTA2 proteins, leading to inhibition of growth arrest and apoptosis. Moreover, hypoxia-inducible factor 1α is also deacetylated and stabilized by MTA1 protein, resulting in stimulation of angiogenesis. MTA1 protein also functions as a coactivator of several genes related to cancer and inflammation. Recent studies clearly show that the MTA family has important roles in epithelial-mesenchymal transitions and DNA damage response. Thus, MTA proteins, especially MTA1, are a possible set of master coregulatory molecules involved in the carcinogenesis and progression of various malignant tumors. MTA proteins are proposed to be important new tools for clinical applications in cancer diagnosis and treatment.

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Abbreviations

ARF:

Alternative reading frame

ATM:

Ataxia teleangiectasia mutated

ATR:

Ataxia teleangiectasia mutated and Rad3-related protein

cDNA:

Complementary DNA

COP1:

Constitutive photomorphogenesis protein 1

DSB:

Double-strand break

EIF5A2:

Eukaryotic initiation factor 5A2

EMT:

Epithelial–mesenchymal transitions

ER:

Estrogen receptor

ERE:

Estrogen-receptor-responsive element

GSK3β:

Glycogen synthase kinase 3β

HBV:

Hepatitis B virus

HCC:

Hepatocellular carcinoma

HDAC:

Histone deacetylase

HIF-1α:

Hypoxia-inducible factor 1α

HMMR:

Hyaluronan-mediated motility receptor

HRG:

Heregulin β1

HSF1:

Heat shock factor 1

IHC:

Immunohistochemistry

15-LOX-1:

15-Lipoxygenase 1

LPS:

Lipopolysaccharide

miR:

microRNA

mRNA:

Messenger RNA

MTA:

Metastasis-associated

MyD88:

Myeloid differentiation primary response gene 88

NuRD:

Nucleosome remodeling and histone deacetylation

PolII:

RNA polymerase II

RNAi:

RNA interference

RT-PCR:

Reverse-transcription polymerase chain reaction

shRNA:

Short hairpin RNA

SUMO:

Small ubiquitin-related modifier

TGF-β1 :

Transforming growth factor β1

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Authors and Affiliations

  1. Department of Gastroenterological Surgery, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan

    Yasushi Toh

  2. Department of Molecular Pathology, The Institute for Molecular Medicine, Huntington Beach, CA, 92647, USA

    Garth L. Nicolson

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  1. Yasushi Toh
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  2. Garth L. Nicolson
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Correspondence to Yasushi Toh .

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  1. Instituto de Ciências Biológicas, Departamento de Bioquímica, Universidade Federal de Minas Gerais, Belo Horizonte, São Paulo, Brazil

    Rodrigo R. Resende

  2. Depto. Bioquímica, Universidade de São Paulo Inst. Química, São Paulo, São Paulo, Brazil

    Henning Ulrich

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Toh, Y., Nicolson, G.L. (2013). Signaling Pathways of MTA Family Proteins as Regulators of Cancer Progression and Metastasis. In: Resende, R., Ulrich, H. (eds) Trends in Stem Cell Proliferation and Cancer Research. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6211-4_10

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