Epithelial to mesenchymal transition in colorectal cancer (WP4239)

Homo sapiens

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 [https://assays.cancer.gov/available_assays?wp_id=WP4239 CPTAC Assay Portal]


Kristina Hanspers , Alex Pico , Andika Tan , Friederike Ehrhart , Finterly Hu , and Eric Weitz


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Homo sapiens




Pathway Ontology

cancer pathway

Disease Ontology

disease of cellular proliferation colorectal cancer

Cell Type Ontology

colon epithelial cell


Label Type Compact URI Comment
Ca2+ Metabolite chebi:29108
MAP2K1 GeneProduct ensembl:ENSG00000169032
FMNL2 GeneProduct ensembl:ENSG00000157827
TWIST1 GeneProduct ensembl:ENSG00000122691
PROX1 GeneProduct ensembl:ENSG00000117707
SMAD4 GeneProduct ensembl:ENSG00000141646
GSK3B GeneProduct ensembl:ENSG00000082701
GDF15 GeneProduct ensembl:ENSG00000130513
PIK3CA GeneProduct ensembl:ENSG00000121879
TMPRSS4 GeneProduct ensembl:ENSG00000137648
RAF1 GeneProduct ensembl:ENSG00000132155
FOXQ1 GeneProduct ensembl:ENSG00000164379
TGFBR1 GeneProduct ensembl:ENSG00000106799
JAG1 GeneProduct ensembl:ENSG00000101384
TUSC3 GeneProduct ensembl:ENSG00000104723
CTNNB1 GeneProduct ensembl:ENSG00000168036
RBPJ GeneProduct ensembl:ENSG00000168214
EIF5A2 GeneProduct ensembl:ENSG00000163577
STRAP GeneProduct ensembl:ENSG00000023734
MAPK3 GeneProduct ensembl:ENSG00000102882
FZD10 GeneProduct ensembl:ENSG00000111432
pre-miR-9-2 GeneProduct ensembl:ENSG00000284447
NUBPL GeneProduct ensembl:ENSG00000151413
WNT16 GeneProduct ensembl:ENSG00000002745
NOTCH1 GeneProduct ensembl:ENSG00000148400
AKT1 GeneProduct ensembl:ENSG00000142208
CDH1 GeneProduct ensembl:ENSG00000039068
HRAS GeneProduct ensembl:ENSG00000174775
CLDN1 GeneProduct ensembl:ENSG00000163347
TP53 GeneProduct ensembl:ENSG00000141510
PDCD6 GeneProduct ensembl:ENSG00000249915
COL4A1 GeneProduct ensembl:ENSG00000187498
MEF2D GeneProduct ensembl:ENSG00000116604
JUP GeneProduct ensembl:ENSG00000173801
TGFB1 GeneProduct ensembl:ENSG00000105329
NRP2 GeneProduct ensembl:ENSG00000118257
TRAF6 GeneProduct ensembl:ENSG00000175104
NR2C2 GeneProduct ensembl:ENSG00000177463
MAP2K3 GeneProduct ensembl:ENSG00000034152
MAP2K6 GeneProduct ensembl:ENSG00000108984
MAP2K4 GeneProduct ensembl:ENSG00000065559
MAPK14 GeneProduct ensembl:ENSG00000112062
MAPK8 GeneProduct ensembl:ENSG00000107643
SHC1 GeneProduct ensembl:ENSG00000160691
GRB2 GeneProduct ensembl:ENSG00000177885
SOS1 GeneProduct ensembl:ENSG00000115904
SOS2 GeneProduct ensembl:ENSG00000100485
KRAS GeneProduct ensembl:ENSG00000133703
MAP2K2 GeneProduct ensembl:ENSG00000126934
MAPK1 GeneProduct ensembl:ENSG00000100030
AKT2 GeneProduct ensembl:ENSG00000105221
AKT3 GeneProduct ensembl:ENSG00000117020
SNAI1 GeneProduct ensembl:ENSG00000124216
SNAI2 GeneProduct ensembl:ENSG00000019549
NOTCH2 GeneProduct ensembl:ENSG00000134250
NOTCH3 GeneProduct ensembl:ENSG00000074181
NOTCH4 GeneProduct ensembl:ENSG00000204301
HIF1A GeneProduct ensembl:ENSG00000100644
JAG2 GeneProduct ensembl:ENSG00000184916
DLL1 GeneProduct ensembl:ENSG00000198719
DLL3 GeneProduct ensembl:ENSG00000090932
DLL4 GeneProduct ensembl:ENSG00000128917
DLK1 GeneProduct ensembl:ENSG00000185559
CDKL2 GeneProduct ensembl:ENSG00000138769
TWIST2 GeneProduct ensembl:ENSG00000233608
CDH2 GeneProduct ensembl:ENSG00000170558
ZEB2 GeneProduct ensembl:ENSG00000169554
FOXC2 GeneProduct ensembl:ENSG00000176692
FOXM1 GeneProduct ensembl:ENSG00000111206
FN1 GeneProduct ensembl:ENSG00000115414
SNAI1 GeneProduct ensembl:ENSG00000124216
SNAI1 GeneProduct ensembl:ENSG00000124216
SNAI1 GeneProduct ensembl:ENSG00000124216
CTDSP1 GeneProduct ensembl:ENSG00000144579
SNAI1 GeneProduct ensembl:ENSG00000124216
PKD1 GeneProduct ensembl:ENSG00000008710
PAK1 GeneProduct ensembl:ENSG00000149269
LATS2 GeneProduct ensembl:ENSG00000150457
TWIST1 GeneProduct ensembl:ENSG00000122691
TWIST2 GeneProduct ensembl:ENSG00000233608
TWIST1 GeneProduct ensembl:ENSG00000122691
TWIST2 GeneProduct ensembl:ENSG00000233608
ZEB2 GeneProduct ensembl:ENSG00000169554
ZEB2 GeneProduct ensembl:ENSG00000169554
SUZ12 GeneProduct ensembl:ENSG00000178691
RBBP4 GeneProduct ensembl:ENSG00000162521
EED GeneProduct ensembl:ENSG00000074266
EZH2 GeneProduct ensembl:ENSG00000106462
ZEB1 GeneProduct ensembl:ENSG00000148516
TGFBR2 GeneProduct ensembl:ENSG00000163513
TGFB2 GeneProduct ensembl:ENSG00000092969
TGFB3 GeneProduct ensembl:ENSG00000119699
MAPK11 GeneProduct ensembl:ENSG00000185386
MAPK13 GeneProduct ensembl:ENSG00000156711
MAPK12 GeneProduct ensembl:ENSG00000188130
SNAI1 GeneProduct ensembl:ENSG00000124216
SMAD2 GeneProduct ensembl:ENSG00000175387
SMAD3 GeneProduct ensembl:ENSG00000166949
DSP GeneProduct ensembl:ENSG00000096696
PKP1 GeneProduct ensembl:ENSG00000081277
PKP2 GeneProduct ensembl:ENSG00000057294
CRB3 GeneProduct ensembl:ENSG00000130545
MPP5 GeneProduct ensembl:ENSG00000072415
VTN GeneProduct ensembl:ENSG00000109072
MMP15 GeneProduct ensembl:ENSG00000102996
MMP2 GeneProduct ensembl:ENSG00000087245
MMP9 GeneProduct ensembl:ENSG00000100985
ID1 GeneProduct ensembl:ENSG00000125968
ID2 GeneProduct ensembl:ENSG00000115738
CDH1 GeneProduct ensembl:ENSG00000039068
OCLN GeneProduct ensembl:ENSG00000197822
DSP GeneProduct ensembl:ENSG00000096696
CDH2 GeneProduct ensembl:ENSG00000170558
FN1 GeneProduct ensembl:ENSG00000115414
VTN GeneProduct ensembl:ENSG00000109072
SPARC GeneProduct ensembl:ENSG00000113140
ITGA5 GeneProduct ensembl:ENSG00000161638
CDH1 GeneProduct ensembl:ENSG00000039068
PKP1 GeneProduct ensembl:ENSG00000081277
PKP2 GeneProduct ensembl:ENSG00000057294
CRB3 GeneProduct ensembl:ENSG00000130545
TJP1 GeneProduct ensembl:ENSG00000104067
CDH2 GeneProduct ensembl:ENSG00000170558
VTN GeneProduct ensembl:ENSG00000109072
OCLN GeneProduct ensembl:ENSG00000197822
CLDN2 GeneProduct ensembl:ENSG00000165376
CLDN3 GeneProduct ensembl:ENSG00000165215
CLDN4 GeneProduct ensembl:ENSG00000189143
CLDN5 GeneProduct ensembl:ENSG00000184113
CLDN6 GeneProduct ensembl:ENSG00000184697
CLDN7 GeneProduct ensembl:ENSG00000181885
CLDN8 GeneProduct ensembl:ENSG00000156284
CLDN9 GeneProduct ensembl:ENSG00000213937
CLDN10 GeneProduct ensembl:ENSG00000134873
CLDN11 GeneProduct ensembl:ENSG00000013297
CLDN12 GeneProduct ensembl:ENSG00000157224
CLDN14 GeneProduct ensembl:ENSG00000159261
CLDN15 GeneProduct ensembl:ENSG00000106404
CLDN16 GeneProduct ensembl:ENSG00000113946
CLDN17 GeneProduct ensembl:ENSG00000156282
CLDN18 GeneProduct ensembl:ENSG00000066405
CLDN19 GeneProduct ensembl:ENSG00000164007
CLDN20 GeneProduct ensembl:ENSG00000171217
CLDN22 GeneProduct ensembl:ENSG00000177300
CLDN23 GeneProduct ensembl:ENSG00000253958
CLDN24 GeneProduct ensembl:ENSG00000185758
COL4A2 GeneProduct ensembl:ENSG00000134871
COL4A3 GeneProduct ensembl:ENSG00000169031
COL4A4 GeneProduct ensembl:ENSG00000081052
COL4A5 GeneProduct ensembl:ENSG00000188153
COL4A6 GeneProduct ensembl:ENSG00000197565
WNT1 GeneProduct ensembl:ENSG00000125084
WNT4 GeneProduct ensembl:ENSG00000162552
WNT2 GeneProduct ensembl:ENSG00000105989
WNT3 GeneProduct ensembl:ENSG00000108379
WNT5A GeneProduct ensembl:ENSG00000114251
WNT6 GeneProduct ensembl:ENSG00000115596
WNT7A GeneProduct ensembl:ENSG00000154764
WNT7B GeneProduct ensembl:ENSG00000188064
WNT8A GeneProduct ensembl:ENSG00000061492
WNT8B GeneProduct ensembl:ENSG00000075290
WNT10B GeneProduct ensembl:ENSG00000169884
WNT11 GeneProduct ensembl:ENSG00000085741
WNT2B GeneProduct ensembl:ENSG00000134245
WNT9A GeneProduct ensembl:ENSG00000143816
WNT9B GeneProduct ensembl:ENSG00000158955
WNT10A GeneProduct ensembl:ENSG00000135925
WNT5B GeneProduct ensembl:ENSG00000111186
WNT3A GeneProduct ensembl:ENSG00000154342
WNT3A GeneProduct ensembl:ENSG00000154342
FZD2 GeneProduct ensembl:ENSG00000180340
FZD5 GeneProduct ensembl:ENSG00000163251
FZD3 GeneProduct ensembl:ENSG00000104290
FZD1 GeneProduct ensembl:ENSG00000157240
FZD4 GeneProduct ensembl:ENSG00000174804
FZD6 GeneProduct ensembl:ENSG00000164930
FZD7 GeneProduct ensembl:ENSG00000155760
FZD8 GeneProduct ensembl:ENSG00000177283
FZD9 GeneProduct ensembl:ENSG00000188763
LRP5 GeneProduct ensembl:ENSG00000162337
LRP6 GeneProduct ensembl:ENSG00000070018
PIK3CB GeneProduct ensembl:ENSG00000051382
PIK3CD GeneProduct ensembl:ENSG00000171608
PIK3R1 GeneProduct ensembl:ENSG00000145675
PIK3R2 GeneProduct ensembl:ENSG00000105647
PIK3R3 GeneProduct ensembl:ENSG00000117461


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