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Molecular mechanisms of ovarian carcinoma metastasis: Key genes and regulatory microRNAs

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Abstract

Metastasis of primary tumors progresses stepwise — from change in biochemistry, morphology, and migratory patterns of tumor cells to the emergence of receptors on their surface that facilitate directional migration to target organs followed by the formation of a specific microenvironment in a target organ that helps attachment and survival of metastatic cells. A set of specific genes and signaling pathways mediate this process under control of microRNA. The molecular mechanisms underlying biological processes associated with tumor metastasis are reviewed in this publication using ovarian cancer, which exhibits high metastatic potential, as an example. Information and data on the genes and regulatory microRNAs involved in the formation of cancer stem cells, epithelial–mesenchymal transition, reducing focal adhesion, degradation of extracellular matrix, increasing migration activity of cancer cells, formation of spheroids, apoptosis, autophagy, angiogenesis, formation of metastases, and development of ascites are presented. Clusters of microRNAs (miR-145, miR-31, miR-506, miR-101) most essential for metastasis of ovarian cancer including the families of microRNAs (miR-200, miR-214, miR-25) with dual role, which is different in different histological types of ovarian cancer, are discussed in detail in a section of the review.

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Abbreviations

AKT:

AKT serine/threonine kinase

AXL:

AXL receptor tyrosine kinase

BDNF:

brain-derived neurotrophic factor

BIM:

Bcl-2 interacting mediator of cell death

CSC:

cancer stem cells

CXCL12:

C-X-C motif chemokine ligand 12

ECM:

extracellular matrix

E2F2:

E2F transcription factor 2

EGFR:

epidermal growth factor receptor

EMT:

epithelial–mesenchymal transition

ERK/MAPK:

mitogen-activated protein kinase

FGFR:

fibroblast growth factor receptor

HIF-1α:

hypoxia-inducible factor 1 alpha subunit

HMGA2:

high-mobility group (non-histone chromosomal) protein isoform I-C

MET:

mesenchymal–epithelial transition

MMP2:

matrix metalloproteinase 2 (gelatinase A, type IV collagenase)

MMP9:

matrix metalloproteinase 9 (gelatinase B)

mTOR:

mammalian target of rapamycin

NF-κB:

nuclear factor kappa B

Notch:

Notch (Drosophila) homolog 1 (translocation-associated)

PDGF:

platelet-derived growth factor

PI3K:

phosphatidylinositol-4,5-bisphosphate 3-kinase

PTEN:

phosphatase and tensin homolog (phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase)

P70S6K:

ribosomal protein S6 kinase

RAC1:

Ras-related C3 botulinum toxin substrate 1

SLUG/SNEIL2:

Slug (chicken homolog), zinc finger protein

SMARCA4/BRG1:

SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4

SNAIL:

Snail family transcriptional repressor

SOX4/9:

SRY (sex determining region Y)-box 4/9 protein

S1P:

sphingosine-1-phosphate

SPHK1:

sphingosine kinase 1

S1PR1/2:

sphingosine-1-phosphate receptor 1/2

TGF-β:

transforming growth factor beta

TP53:

tumor protein P53

TWIST:

Twist family BHLH transcription factor

ULK1:

Unc-51 like autophagy-activating kinase 1

uPA:

urokinase type plasminogen activator

VEGF:

vascular endothelial growth factor

VEGFR:

vascular endothelial growth factor receptor

Wnt:

wingless-type MMTV integration site family

ZBTB10:

zinc finger and BTB domain-containing protein 10

ZEB:

zinc finger E-box binding homeobox 1/2

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Authors and Affiliations

  1. Institute of General Pathology and Pathophysiology, Moscow, 125315, Russia

    E. A. Braga & M. V. Fridman

  2. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 117971, Russia

    M. V. Fridman

  3. Blokhin Cancer Research Center, Moscow, 115478, Russia

    N. E. Kushlinskii

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  1. E. A. Braga
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  2. M. V. Fridman
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  3. N. E. Kushlinskii
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Correspondence to E. A. Braga.

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Original Russian Text © E. A. Braga, M. V. Fridman, N. E. Kushlinskii, 2017, published in Biokhimiya, 2017, Vol. 82, No. 5, pp. 717-731.

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Braga, E.A., Fridman, M.V. & Kushlinskii, N.E. Molecular mechanisms of ovarian carcinoma metastasis: Key genes and regulatory microRNAs. Biochemistry Moscow 82, 529–541 (2017). https://doi.org/10.1134/S0006297917050017

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  • DOI: https://doi.org/10.1134/S0006297917050017

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