KEGG   PATHWAY: hsa05210
hsa05210                    Pathway                                
Colorectal cancer - Homo sapiens (human)
Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes (TSG). Two major mechanisms of genomic instability have been identified in sporadic CRC progression. The first, known as chromosomal instability (CIN), results from a series of genetic changes that involve the activation of oncogenes such as K-ras and inactivation of TSG such as p53, DCC/Smad4, and APC. The second, known as microsatellite instability (MSI), results from inactivation of the DNA mismatch repair genes MLH1 and/or MSH2 by hypermethylation of their promoter, and secondary mutation of genes with coding microsatellites, such as transforming growth factor receptor II (TGF-RII) and BAX. Hereditary syndromes have germline mutations in specific genes (mutation in the tumour suppressor gene APC on chromosome 5q in FAP, mutated DNA mismatch repair genes in HNPCC).
Human Diseases; Cancer: specific types
Pathway map
hsa05210  Colorectal cancer

nt06210  ERK signaling
nt06213  Other RAS signaling
nt06214  PI3K signaling
nt06215  WNT signaling
nt06218  TGFB signaling
nt06231  Apoptosis
nt06240  Transcription
nt06260  Colorectal cancer
nt06261  Gastric cancer
nt06262  Pancreatic cancer
nt06263  Hepatocellular carcinoma
nt06265  Bladder cancer
nt06266  Non-small cell lung cancer
nt06267  Small cell lung cancer
nt06268  Melanoma
nt06269  Basal cell carcinoma
nt06270  Breast cancer
nt06271  Endometrial cancer
nt06273  Glioma
nt06274  Thyroid cancer
nt06275  Acute myeloid leukemia
nt06276  Chronic myeloid leukemia
N00012  Mutation-activated KRAS/NRAS to ERK signaling pathway
N00032  Mutation-activated KRAS/NRAS to PI3K signaling pathway
N00041  EGFR-overexpression to RAS-ERK signaling pathway
N00042  EGFR-overexpression to PI3K signaling pathway
N00057  Mutation-inactivated APC to Wnt signaling pathway
N00058  Mutation-activated CTNNB1 to Wnt signaling pathway
N00064  Mutation-inactivated TGFBR2 to TGF-beta signaling pathway
N00065  Mutation-inactivated SMAD2 to TGF-beta signaling pathway
N00099  Mutation-inactivated BAX to apoptotic pathway
N00102  Loss of DCC to DCC-apoptotic pathway
N00104  Mutation-activated KRAS to RalGDS signaling pathway
N00115  Mutation-inactivated TP53 to transcription
N00230  TGFA-overexpression to RAS-ERK signaling pathway
N00232  TGFA-overexpression to PI3K signaling pathway
N00276  EGF-overexpression to RAS-ERK signaling pathway
N00278  EREG-overexpression to RAS-ERK signaling pathway
N00280  AREG-overexpression to RAS-ERK signaling pathway
N00281  EGF-overexpression to PI3K signaling pathway
N00283  EREG-overexpression to PI3K signaling pathway
N00285  AREG-overexpression to PI3K signaling pathway
H00020  Colorectal cancer
D10137  Regorafenib hydrate (JAN)
D10138  Regorafenib (USAN/INN)
Homo sapiens (human) [GN:hsa]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:]
8312  AXIN1; axin 1 [KO:K02157]
8313  AXIN2; axin 2 [KO:K04385]
1499  CTNNB1; catenin beta 1 [KO:K02105]
324  APC; APC regulator of WNT signaling pathway [KO:K02085]
10297  APC2; APC regulator of WNT signaling pathway 2 [KO:K02085]
6932  TCF7; transcription factor 7 [KO:K02620]
83439  TCF7L1; transcription factor 7 like 1 [KO:K04490]
6934  TCF7L2; transcription factor 7 like 2 [KO:K04491]
51176  LEF1; lymphoid enhancer binding factor 1 [KO:K04492]
332  BIRC5; baculoviral IAP repeat containing 5 [KO:K08731]
4609  MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377]
595  CCND1; cyclin D1 [KO:K04503]
3845  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:]
572  BAD; BCL2 associated agonist of cell death [KO:K02158]
842  CASP9; caspase 9 [KO:K04399] [EC:]
369  ARAF; A-Raf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:]
673  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
3725  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
2353  FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379]
5900  RALGDS; ral guanine nucleotide dissociation stimulator [KO:K08732]
5898  RALA; RAS like proto-oncogene A [KO:K07834]
5899  RALB; RAS like proto-oncogene B [KO:K07835]
5879  RAC1; Rac family small GTPase 1 [KO:K04392]
5880  RAC2; Rac family small GTPase 2 [KO:K07860]
5881  RAC3; Rac family small GTPase 3 [KO:K07861]
387  RHOA; ras homolog family member A [KO:K04513]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:]
1630  DCC; DCC netrin 1 receptor [KO:K06765]
836  CASP3; caspase 3 [KO:K02187] [EC:]
26060  APPL1; adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 [KO:K08733]
7040  TGFB1; transforming growth factor beta 1 [KO:K13375]
7042  TGFB2; transforming growth factor beta 2 [KO:K13376]
7043  TGFB3; transforming growth factor beta 3 [KO:K13377]
7046  TGFBR1; transforming growth factor beta receptor 1 [KO:K04674] [EC:]
7048  TGFBR2; transforming growth factor beta receptor 2 [KO:K04388] [EC:]
4087  SMAD2; SMAD family member 2 [KO:K04500]
4088  SMAD3; SMAD family member 3 [KO:K23605]
4089  SMAD4; SMAD family member 4 [KO:K04501]
4292  MLH1; mutL homolog 1 [KO:K08734]
4436  MSH2; mutS homolog 2 [KO:K08735]
4437  MSH3; mutS homolog 3 [KO:K08736]
2956  MSH6; mutS homolog 6 [KO:K08737]
581  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
5366  PMAIP1; phorbol-12-myristate-13-acetate-induced protein 1 [KO:K10131]
10018  BCL2L11; BCL2 like 11 [KO:K16341]
27113  BBC3; BCL2 binding component 3 [KO:K10132]
596  BCL2; BCL2 apoptosis regulator [KO:K02161]
54205  CYCS; cytochrome c, somatic [KO:K08738]
7157  TP53; tumor protein p53 [KO:K04451]
1026  CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625]
1647  GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402]
4616  GADD45B; growth arrest and DNA damage inducible beta [KO:K04402]
10912  GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402]
578  BAK1; BCL2 antagonist/killer 1 [KO:K14021]
1643  DDB2; damage specific DNA binding protein 2 [KO:K10140]
51426  POLK; DNA polymerase kappa [KO:K03511] [EC:]
1950  EGF; epidermal growth factor [KO:K04357]
7039  TGFA; transforming growth factor alpha [KO:K08774]
2069  EREG; epiregulin [KO:K09784]
374  AREG; amphiregulin [KO:K09782]
1956  EGFR; epidermal growth factor receptor [KO:K04361] [EC:]
2885  GRB2; growth factor receptor bound protein 2 [KO:K04364]
6654  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
6655  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
3265  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
4893  NRAS; NRAS proto-oncogene, GTPase [KO:K07828]
2475  MTOR; mechanistic target of rapamycin kinase [KO:K07203] [EC:]
6198  RPS6KB1; ribosomal protein S6 kinase B1 [KO:K04688] [EC:]
6199  RPS6KB2; ribosomal protein S6 kinase B2 [KO:K04688] [EC:]
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Grady WM.
Genomic instability and colon cancer.
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Soreide K, Janssen EA, Soiland H, Korner H, Baak JP.
Microsatellite instability in colorectal cancer.
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Anwar S, Hall C, White J, Deakin M, Farrell W, Elder JB.
Hereditary non-polyposis colorectal cancer: an updated review.
Eur J Surg Oncol 26:635-45 (2000)
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Colorectal cancer: genetics of development and metastasis.
J Gastroenterol 41:185-92 (2006)
Lynch HT, de la Chapelle A.
Hereditary colorectal cancer.
N Engl J Med 348:919-32 (2003)
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The significance of unstable chromosomes in colorectal cancer.
Nat Rev Cancer 3:695-701 (2003)
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Cancer Metastasis Rev 18:15-30 (1999)
Behrens J.
The role of the Wnt signalling pathway in colorectal tumorigenesis.
Biochem Soc Trans 33:672-5 (2005)
Behrens J, Lustig B.
The Wnt connection to tumorigenesis.
Int J Dev Biol 48:477-87 (2004)
Polakis P.
The adenomatous polyposis coli (APC) tumor suppressor.
Biochim Biophys Acta 1332:F127-47 (1997)
Janssen KP.
Murine models of colorectal cancer: studying the role of oncogenic K-ras.
Cell Mol Life Sci 60:495-506 (2003)
Adjei AA.
Blocking oncogenic Ras signaling for cancer therapy.
J Natl Cancer Inst 93:1062-74 (2001)
Arakawa H.
Netrin-1 and its receptors in tumorigenesis.
Nat Rev Cancer 4:978-87 (2004)
Mehlen P, Fearon ER.
Role of the dependence receptor DCC in colorectal cancer pathogenesis.
J Clin Oncol 22:3420-8 (2004)
Peltomaki P.
DNA mismatch repair and cancer.
Mutat Res 488:77-85 (2001)
Li F, Cao Y, Townsend CM Jr, Ko TC.
TGF-beta signaling in colon cancer cells.
World J Surg 29:306-11 (2005)
Roman C, Saha D, Beauchamp R.
TGF-beta and colorectal carcinogenesis.
Watson AJ.
An overview of apoptosis and the prevention of colorectal cancer.
Crit Rev Oncol Hematol 57:107-21 (2006)
Watson AJ.
Apoptosis and colorectal cancer.
Gut 53:1701-9 (2004)
Houlston RS.
What we could do now: molecular pathology of colorectal cancer.
Mol Pathol 54:206-14 (2001)
Hector S, Prehn JH
Apoptosis signaling proteins as prognostic biomarkers in colorectal cancer: a review.
Biochim Biophys Acta 1795:117-29 (2009)
Karnoub AE, Weinberg RA
Ras oncogenes: split personalities.
Nat Rev Mol Cell Biol 9:517-31 (2008)
Wang D, Xia D, Dubois RN
The Crosstalk of PTGS2 and EGF Signaling Pathways in Colorectal Cancer.
Cancers (Basel) 3:3894-908 (2011)
Dasari A, Messersmith WA
New strategies in colorectal cancer: biomarkers of response to epidermal growth factor receptor monoclonal antibodies and potential therapeutic targets in phosphoinositide 3-kinase and mitogen-activated protein kinase pathways.
Clin Cancer Res 16:3811-8 (2010)
Hutchinson RA, Adams RA, McArt DG, Salto-Tellez M, Jasani B, Hamilton PW
Epidermal growth factor receptor immunohistochemistry: new opportunities in metastatic colorectal cancer.
J Transl Med 13:217 (2015)
hsa04010  MAPK signaling pathway
hsa04012  ErbB signaling pathway
hsa04110  Cell cycle
hsa04115  p53 signaling pathway
hsa04150  mTOR signaling pathway
hsa04151  PI3K-Akt signaling pathway
hsa04210  Apoptosis
hsa04310  Wnt signaling pathway
hsa04350  TGF-beta signaling pathway
KO pathway

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