Epithelial to mesenchymal transition in colorectal cancer (Homo sapiens)

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7, 113433, 735821239333ClaudinsOther effectorsCollagensNucelusColorectal epithelial cellDegradationEpithelial-Mesenchymal TransitionTGFb and Ras/MAPKUbiquitin-mediateddegradationRAF1HRASTGFBR1TUSC3MAP2K1pre-miR-9-2TRAF6PIK3CAGSK3BFMNL2FOXQ1PDCD6ClaudinsCa2+COL4A1CLDN1CytokeratinsRBPJPROX1TGFB1MEF2DMMPsTMPRSS4NRP2MAPK3TWIST1CDH1WNT16JAG1JUPAKT1EIF5A2FZD10Tyrosine kinase receptorsNUBPLCollagenGDF15NOTCH1CTNNB1STRAPTP53SMAD4P1, 14-16PNR2C2MAP2K3MAP2K6MAP2K4MAPK14MAPK8SHC1GRB2SOS1SOS2KRASMAP2K210, 13MAPK1AKT2AKT3SNAI1SNAI2NOTCH2NOTCH3NOTCH43HIF1A3JAG2DLL1DLL3DLL4DLK1CDKL2TWIST2PCDH2ZEB2FOXC2FOXM1FN1SNAI1PSNAI1PPSNAI1PCTDSP1SNAI1PPPKD1PAK1LATS2TWIST1TWIST2PPTWIST1TWIST2ZEB2SumoZEB2SumoSUZ12RBBP4EEDEZH2ZEB1366TGFBR2TGFB2TGFB3MAPK11MAPK13MAPK12SNAI1PSMAD2SMAD3DSPPKP1PKP2CRB3MPP5VTNMMP153MMP2MMP9ID1ID233CDH1ClaudinsOCLNDSPCDH2FN1VTNSPARCITGA5CDH1PKP1PKP2CRB3TJP1CDH2VTNOCLNCLDN2CLDN3CLDN4CLDN5CLDN6CLDN7CLDN8CLDN9CLDN10CLDN11CLDN12CLDN14CLDN15CLDN16CLDN17CLDN18CLDN19CLDN20CLDN22CLDN23CLDN24COL4A2COL4A3COL4A4COL4A5COL4A6WNT1WNT4WNT2WNT3WNT5AWNT6WNT7AWNT7BWNT8AWNT8BWNT10BWNT11WNT2BWNT9AWNT9BWNT10AWNT5BWNT3AWNT3AFZD2FZD5FZD3FZD1FZD4FZD6FZD7FZD8FZD9LRP5LRP6PIK3CBPIK3CDPIK3R1PIK3R2PIK3R3Hypoxia


Description

Epithelial to mesenchymal transition (EMT) is a process during which cells lose their epithelial characteristics, and gain mesenchymal properties, such as increased motility. In colorectal cancer (CRC), EMT is associated with an invasive or metastatic phenotype. During EMT, tumor cells undergo tight junction dissolution, disruption of apical–basal polarity, and reorganization of the cytoskeletal architecture, which enable cells to develop an invasive phenotype. In cancer cells, EMT is abnormally regulated by extracellular stimuli derived from the tumor microenvironment, including growth factors and inflammatory cytokines, along with intra-tumoral physical stresses such as hypoxia. Therefore, EMT programming allows tumor cells to adapt to the constant changes of the human tumor microenvironment, and thus to successfully metastasize. This pathway summarizes the major signaling pathways and inducers that promote EMT in CRC.

A set of core transcription factors regulate EMT: SNAIL family of zinc-finger transcription factors SNAIL/SLUG; the zinc finger E-box binding homeobox (ZEB) family of transcription factors ZEB1/ZEB2, and the TWIST family of basic helix-loop-helix (bHLH) transcription factors TWIST1/TWIST2. (Adapted from Vu et al.) Phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Ontology Terms

 

Bibliography

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  1. Miyaki M, Kuroki T; ''Role of Smad4 (DPC4) inactivation in human cancer.''; Biochem Biophys Res Commun, 2003 PubMed Europe PMC Scholia
  2. Zhang H, Meng F, Liu G, Zhang B, Zhu J, Wu F, Ethier SP, Miller F, Wu G; ''Forkhead transcription factor foxq1 promotes epithelial-mesenchymal transition and breast cancer metastasis.''; Cancer Res, 2011 PubMed Europe PMC Scholia
  3. Vu T, Datta PK; ''Regulation of EMT in Colorectal Cancer: A Culprit in Metastasis.''; Cancers (Basel), 2017 PubMed Europe PMC Scholia
  4. Wang X, Wu F, Wang H, Duan X, Huang R, Tuersuntuoheti A, Su L, Yan S, Zhao Y, Lu Y, Li K, Yao J, Luo Z, Guo L, Liu J, Chen X, Hu H, Li X, Bao M, Bi X, Du B, Miao S, Cai J, Wang L, Zhou H, Ying J, Song W, Zhao H; ''PDCD6 cooperates with C-Raf to facilitate colorectal cancer progression via Raf/MEK/ERK activation.''; J Exp Clin Cancer Res, 2020 PubMed Europe PMC Scholia
  5. Li Q, Wu J, Wei P, Xu Y, Zhuo C, Wang Y, Li D, Cai S; ''Overexpression of forkhead Box C2 promotes tumor metastasis and indicates poor prognosis in colon cancer via regulating epithelial-mesenchymal transition.''; Am J Cancer Res, 2015 PubMed Europe PMC Scholia
  6. Yang C, Chen H, Tan G, Gao W, Cheng L, Jiang X, Yu L, Tan Y; ''FOXM1 promotes the epithelial to mesenchymal transition by stimulating the transcription of Slug in human breast cancer.''; Cancer Lett, 2013 PubMed Europe PMC Scholia
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History

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CompareRevisionActionTimeUserComment
128751view12:36, 21 February 2024EweitzUpgrade disease node
127351view18:25, 20 September 2023Khanspersupdated phospho sites
127236view20:17, 25 August 2023Khanspersadded lit ref and updated description
126531view23:07, 25 May 2023Khanspersupdated phosphorylation interaction type
118997view09:29, 8 June 2021FinterlyRemoved empty Comment
111457view23:37, 10 August 2020KhanspersAdded interaction between PDCD6 and RAF1
108129view10:28, 29 November 2019FehrhartOntology Term : 'cancer pathway' added !
106393view21:28, 28 August 2019KhanspersModified description
105464view05:12, 8 August 2019KhanspersModified description
103784view20:45, 5 April 2019Khanspersunified node size and added lit refs for mutations
97604view12:00, 29 May 2018AMTanOntology Term : 'colon epithelial cell' added !
97583view22:40, 26 May 2018AlexanderPicoModified title
97138view22:02, 30 April 2018Khanspersadded cell label
97137view21:54, 30 April 2018KhanspersModified title
97006view23:30, 25 April 2018KhanspersModified title
96593view23:50, 22 March 2018KhanspersModified description
96592view23:17, 22 March 2018KhanspersOntology Term : 'disease of cellular proliferation' added !
96591view20:56, 22 March 2018KhanspersModified description
96590view20:45, 22 March 2018Khansperswork in progress
96586view16:45, 22 March 2018KhanspersOntology Term : 'colorectal cancer' added !
96585view04:27, 22 March 2018KhanspersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKT1GeneProductENSG00000142208 (Ensembl)
AKT2GeneProductENSG00000105221 (Ensembl)
AKT3GeneProductENSG00000117020 (Ensembl)
CDH1GeneProductENSG00000039068 (Ensembl)
CDH2GeneProductENSG00000170558 (Ensembl)
CDKL2GeneProductENSG00000138769 (Ensembl)
CLDN10GeneProductENSG00000134873 (Ensembl)
CLDN11GeneProductENSG00000013297 (Ensembl)
CLDN12GeneProductENSG00000157224 (Ensembl)
CLDN14GeneProductENSG00000159261 (Ensembl)
CLDN15GeneProductENSG00000106404 (Ensembl)
CLDN16GeneProductENSG00000113946 (Ensembl)
CLDN17GeneProductENSG00000156282 (Ensembl)
CLDN18GeneProductENSG00000066405 (Ensembl)
CLDN19GeneProductENSG00000164007 (Ensembl)
CLDN1GeneProductENSG00000163347 (Ensembl)
CLDN20GeneProductENSG00000171217 (Ensembl)
CLDN22GeneProductENSG00000177300 (Ensembl)
CLDN23GeneProductENSG00000253958 (Ensembl)
CLDN24GeneProductENSG00000185758 (Ensembl)
CLDN2GeneProductENSG00000165376 (Ensembl)
CLDN3GeneProductENSG00000165215 (Ensembl)
CLDN4GeneProductENSG00000189143 (Ensembl)
CLDN5GeneProductENSG00000184113 (Ensembl)
CLDN6GeneProductENSG00000184697 (Ensembl)
CLDN7GeneProductENSG00000181885 (Ensembl)
CLDN8GeneProductENSG00000156284 (Ensembl)
CLDN9GeneProductENSG00000213937 (Ensembl)
COL4A1GeneProductENSG00000187498 (Ensembl)
COL4A2GeneProductENSG00000134871 (Ensembl)
COL4A3GeneProductENSG00000169031 (Ensembl)
COL4A4GeneProductENSG00000081052 (Ensembl)
COL4A5GeneProductENSG00000188153 (Ensembl)
COL4A6GeneProductENSG00000197565 (Ensembl)
CRB3GeneProductENSG00000130545 (Ensembl)
CTDSP1GeneProductENSG00000144579 (Ensembl)
CTNNB1GeneProductENSG00000168036 (Ensembl)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
ClaudinsGeneProduct
CollagenGeneProduct
CytokeratinsGeneProduct
DLK1GeneProductENSG00000185559 (Ensembl)
DLL1GeneProductENSG00000198719 (Ensembl)
DLL3GeneProductENSG00000090932 (Ensembl)
DLL4GeneProductENSG00000128917 (Ensembl)
DSPGeneProductENSG00000096696 (Ensembl)
EEDGeneProductENSG00000074266 (Ensembl)
EIF5A2GeneProductENSG00000163577 (Ensembl)
EZH2GeneProductENSG00000106462 (Ensembl)
FMNL2GeneProductENSG00000157827 (Ensembl)
FN1GeneProductENSG00000115414 (Ensembl)
FOXC2GeneProductENSG00000176692 (Ensembl)
FOXM1GeneProductENSG00000111206 (Ensembl)
FOXQ1GeneProductENSG00000164379 (Ensembl)
FZD10GeneProductENSG00000111432 (Ensembl)
FZD1GeneProductENSG00000157240 (Ensembl)
FZD2GeneProductENSG00000180340 (Ensembl)
FZD3GeneProductENSG00000104290 (Ensembl)
FZD4GeneProductENSG00000174804 (Ensembl)
FZD5GeneProductENSG00000163251 (Ensembl)
FZD6GeneProductENSG00000164930 (Ensembl)
FZD7GeneProductENSG00000155760 (Ensembl)
FZD8GeneProductENSG00000177283 (Ensembl)
FZD9GeneProductENSG00000188763 (Ensembl)
GDF15GeneProductENSG00000130513 (Ensembl)
GRB2GeneProductENSG00000177885 (Ensembl)
GSK3BGeneProductENSG00000082701 (Ensembl)
HIF1AGeneProductENSG00000100644 (Ensembl)
HRASGeneProductENSG00000174775 (Ensembl)
HypoxiaQ105688 (Wikidata)
ID1GeneProductENSG00000125968 (Ensembl)
ID2GeneProductENSG00000115738 (Ensembl)
ITGA5GeneProductENSG00000161638 (Ensembl)
JAG1GeneProductENSG00000101384 (Ensembl)
JAG2GeneProductENSG00000184916 (Ensembl)
JUPGeneProductENSG00000173801 (Ensembl)
KRASGeneProductENSG00000133703 (Ensembl)
LATS2GeneProductENSG00000150457 (Ensembl)
LRP5GeneProductENSG00000162337 (Ensembl)
LRP6GeneProductENSG00000070018 (Ensembl)
MAP2K1GeneProductENSG00000169032 (Ensembl)
MAP2K2GeneProductENSG00000126934 (Ensembl)
MAP2K3GeneProductENSG00000034152 (Ensembl)
MAP2K4GeneProductENSG00000065559 (Ensembl)
MAP2K6GeneProductENSG00000108984 (Ensembl)
MAPK11GeneProductENSG00000185386 (Ensembl)
MAPK12GeneProductENSG00000188130 (Ensembl)
MAPK13GeneProductENSG00000156711 (Ensembl)
MAPK14GeneProductENSG00000112062 (Ensembl)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
MAPK8GeneProductENSG00000107643 (Ensembl)
MEF2DGeneProductENSG00000116604 (Ensembl)
MMP15GeneProductENSG00000102996 (Ensembl)
MMP2GeneProductENSG00000087245 (Ensembl)
MMP9GeneProductENSG00000100985 (Ensembl)
MMPsGeneProduct
MPP5GeneProductENSG00000072415 (Ensembl)
NOTCH1GeneProductENSG00000148400 (Ensembl)
NOTCH2GeneProductENSG00000134250 (Ensembl)
NOTCH3GeneProductENSG00000074181 (Ensembl)
NOTCH4GeneProductENSG00000204301 (Ensembl)
NR2C2GeneProductENSG00000177463 (Ensembl)
NRP2GeneProductENSG00000118257 (Ensembl)
NUBPLGeneProductENSG00000151413 (Ensembl)
OCLNGeneProductENSG00000197822 (Ensembl)
PAK1GeneProductENSG00000149269 (Ensembl)
PDCD6GeneProductENSG00000249915 (Ensembl)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PIK3CBGeneProductENSG00000051382 (Ensembl)
PIK3CDGeneProductENSG00000171608 (Ensembl)
PIK3R1GeneProductENSG00000145675 (Ensembl)
PIK3R2GeneProductENSG00000105647 (Ensembl)
PIK3R3GeneProductENSG00000117461 (Ensembl)
PKD1GeneProductENSG00000008710 (Ensembl)
PKP1GeneProductENSG00000081277 (Ensembl)
PKP2GeneProductENSG00000057294 (Ensembl)
PROX1GeneProductENSG00000117707 (Ensembl)
RAF1GeneProductENSG00000132155 (Ensembl)
RBBP4GeneProductENSG00000162521 (Ensembl)
RBPJGeneProductENSG00000168214 (Ensembl)
SHC1GeneProductENSG00000160691 (Ensembl)
SMAD2GeneProductENSG00000175387 (Ensembl)
SMAD3GeneProductENSG00000166949 (Ensembl)
SMAD4GeneProductENSG00000141646 (Ensembl)
SNAI1GeneProductENSG00000124216 (Ensembl)
SNAI2GeneProductENSG00000019549 (Ensembl)
SOS1GeneProductENSG00000115904 (Ensembl)
SOS2GeneProductENSG00000100485 (Ensembl)
SPARCGeneProductENSG00000113140 (Ensembl)
STRAPGeneProductENSG00000023734 (Ensembl)
SUZ12GeneProductENSG00000178691 (Ensembl)
TGFB1GeneProductENSG00000105329 (Ensembl)
TGFB2GeneProductENSG00000092969 (Ensembl)
TGFB3GeneProductENSG00000119699 (Ensembl)
TGFBR1GeneProductENSG00000106799 (Ensembl)
TGFBR2GeneProductENSG00000163513 (Ensembl)
TJP1GeneProductENSG00000104067 (Ensembl)
TMPRSS4GeneProductENSG00000137648 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
TRAF6GeneProductENSG00000175104 (Ensembl)
TUSC3GeneProductENSG00000104723 (Ensembl)
TWIST1GeneProductENSG00000122691 (Ensembl)
TWIST2GeneProductENSG00000233608 (Ensembl)
Tyrosine kinase receptorsGeneProduct
VTNGeneProductENSG00000109072 (Ensembl)
WNT10AGeneProductENSG00000135925 (Ensembl)
WNT10BGeneProductENSG00000169884 (Ensembl)
WNT11GeneProductENSG00000085741 (Ensembl)
WNT16GeneProductENSG00000002745 (Ensembl)
WNT1GeneProductENSG00000125084 (Ensembl)
WNT2BGeneProductENSG00000134245 (Ensembl)
WNT2GeneProductENSG00000105989 (Ensembl)
WNT3AGeneProductENSG00000154342 (Ensembl)
WNT3GeneProductENSG00000108379 (Ensembl)
WNT4GeneProductENSG00000162552 (Ensembl)
WNT5AGeneProductENSG00000114251 (Ensembl)
WNT5BGeneProductENSG00000111186 (Ensembl)
WNT6GeneProductENSG00000115596 (Ensembl)
WNT7AGeneProductENSG00000154764 (Ensembl)
WNT7BGeneProductENSG00000188064 (Ensembl)
WNT8AGeneProductENSG00000061492 (Ensembl)
WNT8BGeneProductENSG00000075290 (Ensembl)
WNT9AGeneProductENSG00000143816 (Ensembl)
WNT9BGeneProductENSG00000158955 (Ensembl)
ZEB1GeneProductENSG00000148516 (Ensembl)
ZEB2GeneProductENSG00000169554 (Ensembl)
pre-miR-9-2GeneProductENSG00000284447 (Ensembl)

Annotated Interactions

No annotated interactions

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