KEGG PATHWAY: ko05210

PATHWAY: ko05210

Entry

ko05210                     Pathway

Name

Colorectal cancer

Description

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).

Class

Human Diseases; Cancer: specific types

Pathway map

ko05210

Colorectal cancer

Disease

H00020

Colorectal cancer

Orthology

K00922

PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]

K02085

APC; adenomatosis polyposis coli protein

K02105

CTNNB1; catenin beta 1

K02157

AXIN1; axin 1

K02158

BAD; Bcl-2-antagonist of cell death

K02159

BAX; apoptosis regulator BAX

K02161

BCL2; apoptosis regulator Bcl-2

K02187

CASP3; caspase 3 [EC:3.4.22.56]

K02620

TCF7, TCF-1; transcription factor 7

K02649

PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta

K02833

HRAS; GTPase HRas

K03083

GSK3B; glycogen synthase kinase 3 beta [EC:2.7.11.26]

K03099

SOS; son of sevenless

K03511

POLK; DNA polymerase kappa [EC:2.7.7.7]

K04357

EGF; epidermal growth factor

K04361

EGFR, ERBB1; epidermal growth factor receptor [EC:2.7.10.1]

K04364

GRB2; growth factor receptor-bound protein 2

K04365

BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K04366

RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K04368

MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]

K04369

MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]

K04371

ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]

K04377

MYC; Myc proto-oncogene protein

K04379

FOS; proto-oncogene protein c-fos

K04385

AXIN2; axin 2

K04388

TGFBR2; TGF-beta receptor type-2 [EC:2.7.11.30]

K04392

RAC1; Ras-related C3 botulinum toxin substrate 1

K04399

CASP9; caspase 9 [EC:3.4.22.62]

K04402

GADD45; growth arrest and DNA-damage-inducible protein

K04440

JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]

K04448

JUN; transcription factor AP-1

K04451

TP53, P53; tumor protein p53

K04456

AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]

K04490

TCF7L1; transcription factor 7-like 1

K04491

TCF7L2; transcription factor 7-like 2

K04492

LEF1; lymphoid enhancer-binding factor 1

K04500

SMAD2; mothers against decapentaplegic homolog 2

K04501

SMAD4; mothers against decapentaplegic homolog 4

K04503

CCND1; G1/S-specific cyclin-D1

K04513

RHOA; Ras homolog gene family, member A

K04674

TGFBR1, ALK5; TGF-beta receptor type-1 [EC:2.7.11.30]

K04688

RPS6KB; ribosomal protein S6 kinase beta [EC:2.7.11.1]

K06625

CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A

K06765

DCC; deleted in colorectal carcinoma

K07203

MTOR, FRAP, TOR; serine/threonine-protein kinase mTOR [EC:2.7.11.1]

K07827

KRAS, KRAS2; GTPase KRas

K07828

NRAS; GTPase NRas

K07834

RALA; Ras-related protein Ral-A

K07835

RALB; Ras-related protein Ral-B

K07860

RAC2; Ras-related C3 botulinum toxin substrate 2

K07861

RAC3; Ras-related C3 botulinum toxin substrate 3

K08731

BIRC5; baculoviral IAP repeat-containing protein 5

K08732

RALGDS; ral guanine nucleotide dissociation stimulator

K08733

APPL1, DIP13A; DCC-interacting protein 13 alpha

K08734

MLH1; DNA mismatch repair protein MLH1

K08735

MSH2; DNA mismatch repair protein MSH2

K08736

MSH3; DNA mismatch repair protein MSH3

K08737

MSH6; DNA mismatch repair protein MSH6

K08738

CYC; cytochrome c

K08774

TGFA; transforming growth factor, alpha

K08845

ARAF, ARAF1; A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]

K09782

AREG; amphiregulin

K09784

EREG; epiregulin

K10131

PMAIP1, NOXA; phorbol-12-myristate-13-acetate-induced protein 1

K10132

BBC3, PUMA; Bcl-2-binding component 3

K10140

DDB2; DNA damage-binding protein 2

K13375

TGFB1; transforming growth factor beta-1

K13376

TGFB2; transforming growth factor beta-2

K13377

TGFB3; transforming growth factor beta-3

K14021

BAK, BAK1; Bcl-2 homologous antagonist/killer

K16341

BCL2L11, BIM; Bcl-2-like protein 11

K23605

SMAD3; mothers against decapentaplegic homolog 3

Compound

C05981

Phosphatidylinositol-3,4,5-trisphosphate

Reference

PMID:15000146

Authors

Grady WM.

Title

Genomic instability and colon cancer.

Journal

Cancer Metastasis Rev 23:11-27 (2004)
DOI:10.1023/A:1025861527711

Reference

PMID:16555243

Authors

Soreide K, Janssen EA, Soiland H, Korner H, Baak JP.

Title

Microsatellite instability in colorectal cancer.

Journal

Br J Surg 93:395-406 (2006)
DOI:10.1002/bjs.5328

Reference

PMID:11078609

Authors

Anwar S, Hall C, White J, Deakin M, Farrell W, Elder JB.

Title

Hereditary non-polyposis colorectal cancer: an updated review.

Journal

Eur J Surg Oncol 26:635-45 (2000)
DOI:10.1053/ejso.2000.0974

Reference

PMID:16699851

Authors

Takayama T, Miyanishi K, Hayashi T, Sato Y, Niitsu Y.

Title

Colorectal cancer: genetics of development and metastasis.

Journal

J Gastroenterol 41:185-92 (2006)
DOI:10.1007/s00535-006-1801-6

Reference

PMID:12621137

Authors

Lynch HT, de la Chapelle A.

Title

Hereditary colorectal cancer.

Journal

N Engl J Med 348:919-32 (2003)
DOI:10.1056/NEJMra012242

Reference

PMID:12951588

Authors

Rajagopalan H, Nowak MA, Vogelstein B, Lengauer C.

Title

The significance of unstable chromosomes in colorectal cancer.

Journal

Nat Rev Cancer 3:695-701 (2003)
DOI:10.1038/nrc1165

Reference

PMID:10505543

Authors

Behrens J.

Title

Cadherins and catenins: role in signal transduction and tumor progression.

Journal

Cancer Metastasis Rev 18:15-30 (1999)
DOI:10.1023/A:1006200102166

Reference

PMID:16042571

Authors

Behrens J.

Title

The role of the Wnt signalling pathway in colorectal tumorigenesis.

Journal

Biochem Soc Trans 33:672-5 (2005)
DOI:10.1042/BST0330672

Reference

PMID:15349822

Authors

Behrens J, Lustig B.

Title

The Wnt connection to tumorigenesis.

Journal

Int J Dev Biol 48:477-87 (2004)
DOI:10.1387/ijdb.041815jb

Reference

PMID:9196022

Authors

Polakis P.

Title

The adenomatous polyposis coli (APC) tumor suppressor.

Journal

Biochim Biophys Acta 1332:F127-47 (1997)
DOI:10.1016/S0304-419X(97)00008-5

Reference

PMID:12737309

Authors

Janssen KP.

Title

Murine models of colorectal cancer: studying the role of oncogenic K-ras.

Journal

Cell Mol Life Sci 60:495-506 (2003)
DOI:10.1007/s000180300041

Reference

PMID:11459867

Authors

Adjei AA.

Title

Blocking oncogenic Ras signaling for cancer therapy.

Journal

J Natl Cancer Inst 93:1062-74 (2001)
DOI:10.1093/jnci/93.14.1062

Reference

PMID:15573119

Authors

Arakawa H.

Title

Netrin-1 and its receptors in tumorigenesis.

Journal

Nat Rev Cancer 4:978-87 (2004)
DOI:10.1038/nrc1504

Reference

PMID:15310786

Authors

Mehlen P, Fearon ER.

Title

Role of the dependence receptor DCC in colorectal cancer pathogenesis.

Journal

J Clin Oncol 22:3420-8 (2004)
DOI:10.1200/JCO.2004.02.019

Reference

PMID:11223406

Authors

Peltomaki P.

Title

DNA mismatch repair and cancer.

Journal

Mutat Res 488:77-85 (2001)
DOI:10.1016/S1383-5742(00)00058-2

Reference

PMID:15711891

Authors

Li F, Cao Y, Townsend CM Jr, Ko TC.

Title

TGF-beta signaling in colon cancer cells.

Journal

World J Surg 29:306-11 (2005)
DOI:10.1007/s00268-004-7813-6

Reference

PMID:11170304

Authors

Roman C, Saha D, Beauchamp R.

Title

TGF-beta and colorectal carcinogenesis.

Journal

Microsc Res Tech 52:450-7 (2001)
DOI:10.1002/1097-0029(20010215)52:4<450::AID-JEMT1030>3.0.CO;2-O

Reference

PMID:16326109

Authors

Watson AJ.

Title

An overview of apoptosis and the prevention of colorectal cancer.

Journal

Crit Rev Oncol Hematol 57:107-21 (2006)
DOI:10.1016/j.critrevonc.2005.06.005

Reference

PMID:15479695

Authors

Watson AJ.

Title

Apoptosis and colorectal cancer.

Journal

Gut 53:1701-9 (2004)
DOI:10.1136/gut.2004.052704

Reference

PMID:11477132

Authors

Houlston RS.

Title

What we could do now: molecular pathology of colorectal cancer.

Journal

Mol Pathol 54:206-14 (2001)
DOI:10.1136/mp.54.4.206

Reference

PMID:19167459

Authors

Hector S, Prehn JH

Title

Apoptosis signaling proteins as prognostic biomarkers in colorectal cancer: a review.

Journal

Biochim Biophys Acta 1795:117-29 (2009)
DOI:10.1016/j.bbcan.2008.12.002

Reference

PMID:18568040

Authors

Karnoub AE, Weinberg RA

Title

Ras oncogenes: split personalities.

Journal

Nat Rev Mol Cell Biol 9:517-31 (2008)
DOI:10.1038/nrm2438

Reference

PMID:24213116

Authors

Wang D, Xia D, Dubois RN

Title

The Crosstalk of PTGS2 and EGF Signaling Pathways in Colorectal Cancer.

Journal

Cancers (Basel) 3:3894-908 (2011)
DOI:10.3390/cancers3043894

Reference

PMID:20554751

Authors

Dasari A, Messersmith WA

Title

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.

Journal

Clin Cancer Res 16:3811-8 (2010)
DOI:10.1158/1078-0432.CCR-09-2283

Reference

PMID:26149458

Authors

Hutchinson RA, Adams RA, McArt DG, Salto-Tellez M, Jasani B, Hamilton PW

Title

Epidermal growth factor receptor immunohistochemistry: new opportunities in metastatic colorectal cancer.

Journal

J Transl Med 13:217 (2015)
DOI:10.1186/s12967-015-0531-z

Related
pathway

ko04010