Entry
Name
Hepatocellular carcinoma
Description
Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of the rare human neoplasms etiologically linked to viral factors. It has been shown that, after HBV/HCV infection and alcohol or aflatoxin B1 exposure, genetic and epigenetic changes occur. The recurrent mutated genes were found to be highly enriched in multiple key driver signaling processes, including telomere maintenance, TP53, cell cycle regulation, the Wnt/beta-catenin pathway (CTNNB1 and AXIN1), the phosphatidylinositol-3 kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. Recent studies using whole-exome sequencing have revealed recurrent mutations in new driver genes involved in the chromatin remodelling (ARID1A and ARID2) and the oxidative stress (NFE2L2) pathways.
Class
Human Diseases; Cancer: specific types
BRITE hierarchy
Pathway map
Ortholog table
Disease
H00048 Hepatocellular carcinoma
Orthology
K08774 transforming growth factor, alpha
K13769 insulin-like growth factor 2
K04375 ETS domain-containing protein Elk-1
K06279 SHC-transforming protein 1
K17447 SHC-transforming protein 2
K17448 SHC-transforming protein 3
K17449 SHC-transforming protein 4
K04364 growth factor receptor-bound protein 2
K08845 A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04365 B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02158 Bcl-2-antagonist of cell death
K04570 Bcl-2-like 1 (apoptosis regulator Bcl-X)
K04377 Myc proto-oncogene protein
K06618 retinoblastoma-associated protein
K17454 transcription factor E2F1
K09389 transcription factor E2F2
K06620 transcription factor E2F3
K22183 telomerase RNA component
K06625 cyclin-dependent kinase inhibitor 1A
K04402 growth arrest and DNA-damage-inducible protein
K02159 apoptosis regulator BAX
K14021 Bcl-2 homologous antagonist/killer
K10140 DNA damage-binding protein 2
K06621 cyclin-dependent kinase inhibitor 2A
K04503 G1/S-specific cyclin-D1
K13375 transforming growth factor beta-1
K13376 transforming growth factor beta-2
K13377 transforming growth factor beta-3
K04500 mothers against decapentaplegic homolog 2
K23605 mothers against decapentaplegic homolog 3
K04501 mothers against decapentaplegic homolog 4
K03209 wingless-type MMTV integration site family, member 1
K00182 wingless-type MMTV integration site family, member 2
K00312 wingless-type MMTV integration site family, member 3
K00408 wingless-type MMTV integration site family, member 4
K00444 wingless-type MMTV integration site family, member 5
K00445 wingless-type MMTV integration site family, member 6
K00572 wingless-type MMTV integration site family, member 7
K00714 wingless-type MMTV integration site family, member 8
K01064 wingless-type MMTV integration site family, member 9
K01357 wingless-type MMTV integration site family, member 10
K01384 wingless-type MMTV integration site family, member 11
K01558 wingless-type MMTV integration site family, member 16
K03068 low density lipoprotein receptor-related protein 5/6
K02353 segment polarity protein dishevelled
K03069 frequently rearranged in advanced T-cell lymphomas 1
K03096 frequently rearranged in advanced T-cell lymphomas 2
K02085 adenomatosis polyposis coli protein
K04490 transcription factor 7-like 1
K04491 transcription factor 7-like 2
K04492 lymphoid enhancer-binding factor 1
K05638 nuclear factor erythroid 2-related factor 2
K05460 hepatocyte growth factor
K09593 GRB2-associated-binding protein 1
K11650 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D
K22197 BRG1-associated factor 45A
K22198 zinc finger protein neuro-d4/cer-d4
K11653 AT-rich interactive domain-containing protein 1
K11651 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1
K11648 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1
K11649 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily C
K11647 SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A member 2/4 [EC:5.6.2.-]
K11765 AT-rich interactive domain-containing protein 2
K11723 bromodomain-containing protein 7
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Whittaker S, Marais R, Zhu AX
Title
The role of signaling pathways in the development and treatment of hepatocellular carcinoma.
Journal
Reference
Authors
Zucman-Rossi J, Villanueva A, Nault JC, Llovet JM
Title
Genetic Landscape and Biomarkers of Hepatocellular Carcinoma.
Journal
Reference
Authors
Villanueva A, Newell P, Chiang DY, Friedman SL, Llovet JM.
Title
Genomics and signaling pathways in hepatocellular carcinoma.
Journal
Reference
Authors
Breuhahn K, Longerich T, Schirmacher P
Title
Dysregulation of growth factor signaling in human hepatocellular carcinoma.
Journal
Reference
Authors
Minguez B, Tovar V, Chiang D, Villanueva A, Llovet JM
Title
Pathogenesis of hepatocellular carcinoma and molecular therapies.
Journal
Reference
Authors
Kudo M
Title
Signaling pathway and molecular-targeted therapy for hepatocellular carcinoma.
Journal
Reference
Authors
Nault JC, Zucman-Rossi J
Title
Genetics of hepatocellular carcinoma: the next generation.
Journal
Reference
Authors
Rocken C, Carl-McGrath S.
Title
Pathology and pathogenesis of hepatocellular carcinoma.
Journal
Reference
Authors
Cornella H, Alsinet C, Villanueva A
Title
Molecular pathogenesis of hepatocellular carcinoma.
Journal
Reference
Authors
Niu ZS, Niu XJ, Wang WH
Title
Genetic alterations in hepatocellular carcinoma: An update.
Journal
Reference
Authors
Tannapfel A, Wittekind C
Title
Genes involved in hepatocellular carcinoma: deregulation in cell cycling and apoptosis.
Journal
Reference
Authors
Shiraha H, Yamamoto K, Namba M
Title
Human hepatocyte carcinogenesis (review).
Journal
Reference
Authors
Nault JC, Mallet M, Pilati C, Calderaro J, Bioulac-Sage P, Laurent C, Laurent A, Cherqui D, Balabaud C, Zucman-Rossi J
Title
High frequency of telomerase reverse-transcriptase promoter somatic mutations in hepatocellular carcinoma and preneoplastic lesions.
Journal
Reference
Authors
Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB, Calderaro J, Bioulac-Sage P, Letexier M, Degos F, Clement B, Balabaud C, Chevet E, Laurent A, Couchy G, Letouze E, Calvo F, Zucman-Rossi J
Title
Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma.
Journal
Reference
Authors
Praslicka BJ, Kerins MJ, Ooi A
Title
The complex role of NRF2 in cancer: a genomic view
Journal
Reference
Authors
Kansanen E, Kuosmanen SM, Leinonen H, Levonen AL
Title
The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer.
Journal
Reference
Authors
Taguchi K, Motohashi H, Yamamoto M
Title
Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution.
Journal
Reference
Authors
Klaunig JE, Kamendulis LM, Hocevar BA
Title
Oxidative stress and oxidative damage in carcinogenesis.
Journal
Reference
Authors
Krupp G, Bonatz G, Parwaresch R
Title
Telomerase, immortality and cancer.
Journal
Reference
Authors
Jafri MA, Ansari SA, Alqahtani MH, Shay JW
Title
Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies.
Journal
Reference
Authors
Shay JW
Title
Role of Telomeres and Telomerase in Aging and Cancer.
Journal
Reference
Authors
Granito A, Guidetti E, Gramantieri L
Title
c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma.
Journal
Reference
Authors
Vita M, Henriksson M
Title
The Myc oncoprotein as a therapeutic target for human cancer.
Journal
Reference
Authors
Qu A, Jiang C, Cai Y, Kim JH, Tanaka N, Ward JM, Shah YM, Gonzalez FJ
Title
Role of Myc in hepatocellular proliferation and hepatocarcinogenesis.
Journal
Related pathway
ko04932 Non-alcoholic fatty liver disease
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