Epithelial-Mesenchymal Transition and Metastasis under the Control of Transforming Growth Factor β
Abstract
:1. Introduction
2. Regulation of EMT by TGF-β
2.1. Regulation of ECM Gene Expression by TGFβ
2.2. Regulation of Cell Contacts by TGFβ Signaling
2.3. Regulation of the Actin-Based Cytoskeleton during TGFβ-Induced EMT
2.4. TGFβ Controls the Expression of Many Other Growth Factors and Cytokines
3. Regulation of EMT-TF Expression and Activity by TGFβ
4. Regulation of EMT by miRNAs, lncRNAs, and mRNA Translational Mechanisms
5. The Importance of EMT in Tumor Metastasis
6. New Approaches Towards the Treatment of Metastasis
7. Concluding Remarks
Acknowledgments
Conflicts of interest
Abbreviations
4Ei-1 | eIF4E inhibitor 1 |
ADCY9 | adenylyl cyclase 9 |
AGO2 | argonaute 2 |
Akt (1, 2, 3) | oncogene Akt serine/threonine kinase 1, 2, 3 (alias: protein kinase B, PKB) |
AP-1 | activator protein 1 |
ASPP2 | apoptosis-stimulating protein of p53-2 |
ANGPTL4 | angiopoetin-like 4 |
BMP | bone morphogenetic protein |
CAF | cancer-associated fibroblast |
CD51 | cell differentiation 51, alias: integrin αv |
CD61 | cell differentiation 61, alias: integrin β3 |
CD106 | cell differentiation 106, alias: vascular cell adhesion molecule-1, VCAM-1 |
CdGAP | Cdc42 GTPase-activating protein |
CDH1 | E-cadherin |
CDH2 | N-cadherin |
CDK2 | cyclin-dependent kinase 2 |
ceRNA | competing endogenous RNA |
CITED1 | Cbp/p300-interacting transactivator 1 |
Cnt3 | concentrating nucleoside transporter 3 |
CpG | cytosine-phosphate-guanine nukleotide |
CRB3 | Crumbs3 |
CRC | colorectal cancer |
Cre | cyclization recombinase |
CREB1 | cAMP-responsive element binding protein 1 |
CRTC1 | CREB regulated transcription coactivator 1 |
CSC | cancer stem cell |
CtBP | c-terminal-binding protein |
CTC | circulating tumor cell |
CUBIC | clear, unobstructed brain/body imaging cocktails and computational analysis |
CXCL | C-X-C motif chemokine ligand |
Dab2 | disabled-2 |
DUB | deubiquitinase |
ECM | extracellular matrix |
eEF1A1 | eukaryotic elongation factor 1A1 |
EGF | epidermal growth factor |
EMT | epithelial-mesenchymal transition |
EMT-TFs | EMT transcription factors |
EndMT | endothelial-mesenchymal transition |
ENT1 | equilibrative nucleoside transporter 1 |
EpCam | epithelial cell adhesion molecule |
ERK2 | extracellular signal regulated kinase 2 |
ESRP | epithelial splicing regulatory protein |
ETS2 | ETS proto-oncogene 2 |
Fbxo45 | F-box homologue 45 |
FLT3 | Fms-related tyrosine kinase 3 |
FN1 | fibronectin 1 |
Fos | FBJ osteosarcoma oncogene |
Fra-1 | Fos-related antigen 1 |
Fsp1 | fibroblast-specific protein 1 |
GEF-H1 | guanine exchange factor H1 |
GFP | green fluorescent protein |
GM-CSF | granulocyte-monocyte colony stimulating factor |
GPNMB | glycoprotein nmb |
GSK3β | glycogen synthase kinase 3β |
H3K4 | histone 3, lysine 4 |
H3K27me | histone 3, lysine 27, methylation |
HAS2 | hyaluronan synthase 2 |
HDAC1 | histone deacetylase 1 |
Hic-5 | hydrogen peroxide-inducible clone 5 |
HIF | hypoxia-inducible factor |
HMGA2 | high mobility group A2 |
HMLE | human mammary epithelial cells immortalized with the large T antigen |
HNF4 | hepatocyte nuclear factor 4 |
hnRNPE1 | heterogeneous ribonucleoprotein E1 |
Id1/2 | inhibitor of differentiation 1/2 |
IL-11 | interleukin 11 |
ILEI | interleukin-like EMT-inducer |
I-Smad | inhibitory Smad |
ITGA1 | integrin α1 |
JMJD3 | Jumonji domain-containing protein 3 |
JNK | Jun N-terminal kinase |
Jun | Jun proto-oncogene |
Klf4 | Krüppel-like factor 4 |
KPC | K-Ras and mutant p53 pancreatic carcinoma mouse model |
LARG | leukemia-associated Rho guanine nucleotide exchange factor |
Lgr4 | leucine-rich repeat-containing G protein-coupled receptor 4 |
lncRNA | long non-coding RNA |
lncRNA-ATB | lncRNA-induced by TGFβ |
lncRNA-HIT | HOXa transcript induced by TGFβ |
LOXL2 | lysyl oxidase-like 2 |
LSD1 | lysine-specific histone demethylase 1, alias: KDM1A |
MAF | musculoaponeurotic fibrosarcoma |
MAFK | MAF oncogene family protein K |
Malat1 | metastasis associated in lung adenocarcinoma transcript-1 |
MAP-kinase | mitogen-activated protein kinase |
MAPK1 | MAP-kinase 1 |
MDM2 | mouse double minute 2 homolog |
MEKK2 | mitogen-activated protein kinase kinase kinase 2 |
MET | mesenchymal-epithelial transition |
MIG6 | mitogen-inducible gene 6 |
MiRNA | micro-RNA |
MMP | matrix metalloprotease |
MMTV-PyMT | mouse mammary tumor virus polyoma virus middle T antigen |
MOF | males absent on the first (alias: KAT8, lysine acetyltransferase 8) |
MT1-MMP | membrane type I-matrix metalloprotease |
MYCBP | Myc binding protein |
Net1 | neuroepithelial cell transforming 1 |
NF-κB | nuclear factor-κB |
Nkx2.8 | Nk2 homeobox 2.8 |
PAI-1 | plasminogen activator inhibitor 1 |
Par3/6 | partitioning-defective 3/6 |
Pc2 | polycomb protein 2 |
PDGF | platelet-derived growth factor |
PIAS | protein inhibitor of activated Stat |
PMEPAI | prostate transmembrane protein androgen induced-1 |
PRC1/2 | polycomb-repressive complex 1 and 2 |
PTBP3 | polypyrimidine tract binding protein 3 |
R-Smad | receptor-activated Smad |
Rad17 | radiation-induced 17 (alias: checkpoint clamp loader component) |
RFP | red fluorescent protein |
Rho | Ras homologue |
RISC | RNA-induced silencing complex |
RING | really interesting new gene |
RNF8 | RING finger 8 |
ROS | reactive oxygen species |
RTK | receptor tyrosine kinase |
SAE1/2 | SUMO1 activating enzyme subunit 1 |
Shh | sonic hedegehog |
Siah | seven in absentia homolog |
SIK1 | salt-inducible kinase 1 |
Smurf | Smad ubiquitylation regulatory factor |
SND1 | staphylococcal nuclease and tudor domain containing 1 |
SNAG | Snail1/Gfi-1 |
Sox5 | SRY-related high-mobility-group box 5 |
SPRY | SP1a and the Ryanodine Receptor |
Src | (Rous) sarcoma (virus oncogene) |
STAT | signal transducer and activator of transcription |
SUMO | small ubiquitin-related modifier |
Suz12 | suppressor of zeste 12 |
TAK1 | TGFβ-activated kinase 1 |
TAZ | transcriptional coactivator with a PDZ-binding domain |
TF | transcription factor |
TGFβ | transforming growth factor β |
TGIF | TGFβ-induced factor homeobox 1 |
TIC | tumor initiating cell |
TNBC | triple-negative breast cancer |
TNFα | tumor necrosis factor-α |
TOP1 | topoisomerase 1 |
TRAF | TNFα receptor-associated factor |
β-TrCP | β-transducin repeats-containing protein |
Trx | thioredoxin |
TXNIP | thioredoxin-interacting protein |
UBC9 | ubiquitin-conjugating enzyme 9 |
USP | ubiquitin-specific protease |
UTR | untranslated region |
Wnt | wingless and integration site |
YAP | Yes-associated protein |
ZEB1/2 | zinc finger E-box binding homeobox 1/2 |
ZO | zonula occludens |
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Tsubakihara, Y.; Moustakas, A. Epithelial-Mesenchymal Transition and Metastasis under the Control of Transforming Growth Factor β. Int. J. Mol. Sci. 2018, 19, 3672. https://doi.org/10.3390/ijms19113672
Tsubakihara Y, Moustakas A. Epithelial-Mesenchymal Transition and Metastasis under the Control of Transforming Growth Factor β. International Journal of Molecular Sciences. 2018; 19(11):3672. https://doi.org/10.3390/ijms19113672
Chicago/Turabian StyleTsubakihara, Yutaro, and Aristidis Moustakas. 2018. "Epithelial-Mesenchymal Transition and Metastasis under the Control of Transforming Growth Factor β" International Journal of Molecular Sciences 19, no. 11: 3672. https://doi.org/10.3390/ijms19113672