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Biochemistry (Moscow)

, Volume 82, Issue 5, pp 529–541 | Cite as

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

  • E. A. BragaEmail author
  • M. V. Fridman
  • N. E. Kushlinskii
Review

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.

Keywords

regulatory miRNAs key genes ovarian cancer metastasis 

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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Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  • E. A. Braga
    • 1
    Email author
  • M. V. Fridman
    • 1
    • 2
  • N. E. Kushlinskii
    • 3
  1. 1.Institute of General Pathology and PathophysiologyMoscowRussia
  2. 2.Vavilov Institute of General GeneticsRussian Academy of SciencesMoscowRussia
  3. 3.Blokhin Cancer Research CenterMoscowRussia

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