KEGG   PATHWAY: lve05207
Entry
lve05207                    Pathway                                
Name
Chemical carcinogenesis - receptor activation - Lipotes vexillifer (Yangtze River dolphin)
Description
Carcinogenesis is a multistage process that consists of initiation, promotion, and progression stages. Chemicals or environmental factors may act at any of these stages to induce and/or enhance the carcinogenic process. Based on their mode-of-action, carcinogens can be classified as genotoxic or non-genotoxic. Genotoxic agent begins their action at the deoxyribonucleic acid (DNA) level, causing DNA damage through several mechanisms. Non-genotoxic carcinogens are chemicals that cause the development of tumors through multiple non-genotoxic events and epigenetic alterations without direct interaction with DNA. One non-genotoxic mechanism involves receptor activation. Biological mechanisms involving receptor activation fall into two broad categories: (i) those that involve cell surface receptors and some intracellular receptors that activate signal transduction pathways, resulting in biological responses, including gene transcription, and (ii) those that involve intracellular receptors that translocate into the nucleus and act as transcription factors regulating gene expression. Both classes of receptors can be involved in mechanisms of carcinogenesis.
Class
Human Diseases; Cancer: overview
Pathway map
lve05207  Chemical carcinogenesis - receptor activation
lve05207

Organism
Lipotes vexillifer (Yangtze River dolphin) [GN:lve]
Gene
103084703  neuronal acetylcholine receptor subunit alpha-7-like [KO:K04809]
103072843  ARRB1; beta-arrestin-1 [KO:K04439]
103072490  ARRB2; beta-arrestin-2 isoform X1 [KO:K04439]
103072342  SRC; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:2.7.10.2]
103087933  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103072166  RB1; retinoblastoma-associated protein isoform X1 [KO:K06618]
103070408  E2F1; transcription factor E2F1 [KO:K17454]
103072055  BIRC5; baculoviral IAP repeat-containing protein 5 [KO:K08731]
103085092  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
103081981  CDC6; cell division control protein 6 homolog [KO:K02213]
103085456  CDC25A; M-phase inducer phosphatase 1 isoform X1 [KO:K06645] [EC:3.1.3.48]
103076804  JAK2; tyrosine-protein kinase JAK2 [KO:K04447] [EC:2.7.10.2]
103086495  STAT3; signal transducer and activator of transcription 3 [KO:K04692]
103080924  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
103090612  CCND1; G1/S-specific cyclin-D1 [KO:K04503]
103085907  CHRNA4; neuronal acetylcholine receptor subunit alpha-4 [KO:K04806]
103077541  CHRNB2; neuronal acetylcholine receptor subunit beta-2 [KO:K04813]
103090293  CHRNA3; neuronal acetylcholine receptor subunit alpha-3 [KO:K04805]
103069815  CHRNB4; LOW QUALITY PROTEIN: neuronal acetylcholine receptor subunit beta-4 [KO:K04815]
103087340  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
103074544  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
103082192  CACNA1F; voltage-dependent L-type calcium channel subunit alpha-1F isoform X1 [KO:K04853]
103090575  CACNA1S; voltage-dependent L-type calcium channel subunit alpha-1S [KO:K04857]
103073411  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B [KO:K04849]
103068318  CACNA1A; voltage-dependent P/Q-type calcium channel subunit alpha-1A [KO:K04344]
103089257  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103088756  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103085303  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103070370  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103078725  PIK3R3; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103083960  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103084975  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103076365  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103068921  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103083889  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
103068644  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
103087304  RELA; transcription factor p65 isoform X1 [KO:K04735]
103076043  HRAS; GTPase HRas isoform X1 [KO:K02833]
103077579  KRAS; GTPase KRas [KO:K07827]
103068734  NRAS; GTPase NRas [KO:K07828]
103082805  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
103090769  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103070260  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
103075543  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103084433  FOS; proto-oncogene c-Fos isoform X1 [KO:K04379]
103072956  uncharacterized protein LOC103072956 [KO:K04379]
103071861  JUN; transcription factor AP-1 [KO:K04448]
103089962  MYC; myc proto-oncogene protein isoform X1 [KO:K04377]
103077294  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
103073028  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
103090549  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
103086653  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
103089095  VEGFA; vascular endothelial growth factor A isoform X1 [KO:K05448]
103090898  FGF2; LOW QUALITY PROTEIN: fibroblast growth factor 2 [KO:K18497]
103082012  ADRB1; beta-1 adrenergic receptor [KO:K04141]
103071524  ADRB2; beta-2 adrenergic receptor [KO:K04142]
103074465  ADRB3; LOW QUALITY PROTEIN: beta-3 adrenergic receptor [KO:K04143]
103089051  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas-like [KO:K04632]
103085385  neuroendocrine secretory protein 55-like [KO:K04632]
103081539  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
103084817  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
103076182  ADCY3; adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
103075499  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
103091169  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
103075153  ADCY6; adenylate cyclase type 6 isoform X1 [KO:K08046] [EC:4.6.1.1]
103078677  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
103085845  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
103070451  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
103077464  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
103074112  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
103075978  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
103089070  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
103083306  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
103086171  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
103085711  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
103087008  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
103091030  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
103071696  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
103081811  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
103069101  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
103080185  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
103077308  GNAI2; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
103081367  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
103083608  BAD; bcl2 antagonist of cell death [KO:K02158]
103091556  CHRNA9; neuronal acetylcholine receptor subunit alpha-9 [KO:K04810]
103072575  RPS6KA6; ribosomal protein S6 kinase alpha-6 isoform X1 [KO:K04373] [EC:2.7.11.1]
103086828  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
103078586  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
103087256  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X1 [KO:K04373] [EC:2.7.11.1]
103069191  ESR1; estrogen receptor [KO:K08550]
103068725  ESR2; estrogen receptor beta [KO:K08551]
103079238  VDR; vitamin D3 receptor isoform X1 [KO:K08539]
103072491  CCND3; G1/S-specific cyclin-D3 isoform X1 [KO:K10152]
103071962  EGFR; epidermal growth factor receptor isoform X1 [KO:K04361] [EC:2.7.10.1]
103079766  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
103079242  SOS1; son of sevenless homolog 1 [KO:K03099]
103081084  SOS2; son of sevenless homolog 2-like [KO:K03099]
103074746  EIF4EBP1; eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205]
103090358  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
103073645  RPS6KB2; ribosomal protein S6 kinase beta-2 [KO:K04688] [EC:2.7.11.1]
103069468  PAQR7; membrane progestin receptor alpha [KO:K25039]
103084119  PAQR8; membrane progestin receptor beta [KO:K25040]
103082271  PAQR5; membrane progestin receptor gamma [KO:K25041]
103075485  progesterone receptor-like isoform X1 [KO:K08556]
103074658  TNFSF11; tumor necrosis factor ligand superfamily member 11 [KO:K05473]
103082535  STAT5A; signal transducer and activator of transcription 5A isoform X1 [KO:K11223]
103082258  STAT5B; LOW QUALITY PROTEIN: signal transducer and activator of transcription 5B [KO:K11224]
103087600  BCL6; B-cell lymphoma 6 protein isoform X1 [KO:K15618]
103083087  KLF5; Krueppel-like factor 5 isoform X1 [KO:K09206]
103070688  KLF4; Krueppel-like factor 4-like isoform X1 [KO:K17846]
103078640  WNT1; proto-oncogene Wnt-1 [KO:K03209]
103083591  NOTCH2; neurogenic locus notch homolog protein 2-like [KO:K20994]
103089749  JAG1; protein jagged-1 [KO:K06052]
103084450  AR; androgen receptor [KO:K08557]
103073883  EGF; pro-epidermal growth factor isoform X1 [KO:K04357]
103069327  FGF5; fibroblast growth factor 5 [KO:K04358]
103077422  FGF6; fibroblast growth factor 6 [KO:K04358]
103091027  FGF20; fibroblast growth factor 20 [KO:K04358]
103088257  FGF17; fibroblast growth factor 17 isoform X1 [KO:K04358]
103086359  FGF7; fibroblast growth factor 7 [KO:K04358]
103069069  FGF8; fibroblast growth factor 8 isoform X1 [KO:K04358]
103087751  FGF22; LOW QUALITY PROTEIN: fibroblast growth factor 22 [KO:K04358]
103083967  FGF10; fibroblast growth factor 10 [KO:K04358]
103072981  FGF16; fibroblast growth factor 16 [KO:K04358]
103080890  FGF3; LOW QUALITY PROTEIN: fibroblast growth factor 3 [KO:K04358]
103091045  FGF9; fibroblast growth factor 9 [KO:K04358]
103090085  FGF4; fibroblast growth factor 4 [KO:K04358]
103071879  FGF18; fibroblast growth factor 18 [KO:K04358]
103072496  DLL4; delta-like protein 4 [KO:K06051]
103082526  DLL1; delta-like protein 1 [KO:K06051]
103070090  DLL3; LOW QUALITY PROTEIN: delta-like protein 3 [KO:K06051]
103077143  PTGES3; prostaglandin E synthase 3 isoform X1 [KO:K15730] [EC:5.3.99.3]
103071910  AIP; AH receptor-interacting protein [KO:K17767]
103072004  AIPL1; aryl-hydrocarbon-interacting protein-like 1 [KO:K17767]
103071592  AHR; LOW QUALITY PROTEIN: aryl hydrocarbon receptor [KO:K09093]
103087641  HSP90AA1; heat shock protein HSP 90-alpha [KO:K04079]
103068450  HSP90AB1; heat shock protein HSP 90-beta isoform X1 [KO:K04079]
103081131  HSP90B1; endoplasmin [KO:K09487]
103071542  KPNA1; importin subunit alpha-5 [KO:K23940]
103081048  KPNA2; importin subunit alpha-1 isoform X1 [KO:K15043]
103069234  KPNA7; importin subunit alpha-8 [KO:K15043]
103080254  KPNA3; importin subunit alpha-4 [KO:K23583]
103081225  KPNA4; importin subunit alpha-3 [KO:K23583]
103085057  KPNA5; importin subunit alpha-6 isoform X1 [KO:K15042]
103090269  KPNA6; importin subunit alpha-7 isoform X1 [KO:K15042]
103089031  KPNB1; importin subunit beta-1 isoform X1 [KO:K14293]
103075373  ARNT; aryl hydrocarbon receptor nuclear translocator isoform X1 [KO:K09097]
103071513  cytochrome P450 1A1-like [KO:K07408] [EC:1.14.14.1]
103083349  cytochrome P450 1B1-like [KO:K07410] [EC:1.14.14.1]
103074317  EPHX1; epoxide hydrolase 1 [KO:K01253] [EC:3.3.2.9]
103082628  EPHX2; bifunctional epoxide hydrolase 2 [KO:K08726] [EC:3.3.2.10 3.1.3.76]
103086935  EPHX3; epoxide hydrolase 3 [KO:K22368] [EC:3.3.2.10]
103072261  EPHX4; epoxide hydrolase 4 [KO:K22369] [EC:3.3.-.-]
103076713  MGST1; microsomal glutathione S-transferase 1 [KO:K00799] [EC:2.5.1.18]
103081051  MGST3; microsomal glutathione S-transferase 3 [KO:K00799] [EC:2.5.1.18]
103078333  GSTM3; glutathione S-transferase Mu 3 [KO:K00799] [EC:2.5.1.18]
103078618  GSTM1; LOW QUALITY PROTEIN: glutathione S-transferase mu 1 [KO:K00799] [EC:2.5.1.18]
103081925  glutathione S-transferase theta-1-like [KO:K00799] [EC:2.5.1.18]
103082472  glutathione S-transferase theta-1-like [KO:K00799] [EC:2.5.1.18]
103087449  GSTO1; glutathione S-transferase omega-1 isoform X1 [KO:K00799] [EC:2.5.1.18]
103087887  GSTO2; glutathione S-transferase omega-2 isoform X1 [KO:K00799] [EC:2.5.1.18]
103085403  GSTA2; glutathione S-transferase A2 [KO:K00799] [EC:2.5.1.18]
103085685  GSTA4; glutathione S-transferase A4 [KO:K00799] [EC:2.5.1.18]
103071326  MGST2; LOW QUALITY PROTEIN: microsomal glutathione S-transferase 2 [KO:K00799] [EC:2.5.1.18]
103082194  glutathione S-transferase theta-4-like [KO:K00799] [EC:2.5.1.18]
103071327  UDP-glucuronosyltransferase 1-3-like [KO:K00699] [EC:2.4.1.17]
103078119  UGT1A1; UDP-glucuronosyltransferase 1-1 [KO:K00699] [EC:2.4.1.17]
103078627  UDP-glucuronosyltransferase 2C1-like [KO:K00699] [EC:2.4.1.17]
103081112  UGT2B4; LOW QUALITY PROTEIN: UDP glucuronosyltransferase 2 family, polypeptide B4 [KO:K00699] [EC:2.4.1.17]
103071045  UGT1A10; UDP-glucuronosyltransferase 1-10 [KO:K00699] [EC:2.4.1.17]
103086417  NR1I3; LOW QUALITY PROTEIN: nuclear receptor subfamily 1 group I member 3 [KO:K08541]
103083851  RXRA; retinoic acid receptor RXR-alpha isoform X1 [KO:K08524]
103087387  RXRB; retinoic acid receptor RXR-beta isoform X1 [KO:K08525]
103081591  RXRG; retinoic acid receptor RXR-gamma [KO:K08526]
103081108  cytochrome P450 3A29-like [KO:K07424] [EC:1.14.14.1]
103071784  cytochrome P450 1A2-like [KO:K07409] [EC:1.14.14.1]
103083032  PPARA; peroxisome proliferator-activated receptor alpha [KO:K07294]
Compound
C00076  Calcium cation
C00410  Progesterone
C00547  L-Noradrenaline
C00575  3',5'-Cyclic AMP
C00745  Nicotine
C00780  Serotonin
C00788  L-Adrenaline
C00951  Estradiol-17beta
C03690  Bis(2-ethylhexyl)phthalate
C04623  DDT
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C06697  Arsenite
C06790  Trichloroethene
C06916  Clofibrate
C07020  Gemfibrozil
C07434  Phenobarbital
C07535  Benzo[a]pyrene
C07557  2,3,7,8-Tetrachlorodibenzodioxin
C08150  Medroxyprogesterone acetate
C11042  Hexachlorobenzene
C11150  Trichloroacetate
C11371  Nafenopin
C11906  Sodium arsenite
C13624  Bisphenol A
C14240  Di(2-ethylhexyl) adipate
C14573  3,3',4,4',5-Pentachlorobiphenyl
C15995  Bombesin
C16452  N'-Nitrosonornicotine
C16453  4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone
Reference
PMID:15660110
  Authors
Luch A.
  Title
Nature and nurture - lessons from chemical carcinogenesis.
  Journal
Nat Rev Cancer 5:113-25 (2005)
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Reference
PMID:19631282
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Mutat Res 682:94-109 (2009)
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Reference
PMID:21444681
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Wu CH, Lee CH, Ho YS
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Nicotinic acetylcholine receptor-based blockade: applications of molecular targets for cancer therapy.
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Clin Cancer Res 17:3533-41 (2011)
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PMID:19194381
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Is cancer triggered by altered signalling of nicotinic acetylcholine receptors?
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Nat Rev Cancer 9:195-205 (2009)
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PMID:21541211
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Singh S, Pillai S, Chellappan S
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Nicotinic acetylcholine receptor signaling in tumor growth and metastasis.
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J Oncol 2011:456743 (2011)
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PMID:31956359
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Cheng WL, Chen KY, Lee KY, Feng PH, Wu SM
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Nicotinic-nAChR signaling mediates drug resistance in lung cancer.
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J Cancer 11:1125-1140 (2020)
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PMID:24827506
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Connections of nicotine to cancer.
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Nat Rev Cancer 14:419-29 (2014)
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PMID:24398389
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PMID:21640716
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Nicotinic acetylcholine receptor-mediated mechanisms in lung cancer.
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Biochem Pharmacol 82:1015-21 (2011)
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PMID:18262664
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Trends Pharmacol Sci 29:151-8 (2008)
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Cancers (Basel) 6:1138-56 (2014)
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Lung carcinoma signaling pathways activated by smoking.
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Chin J Cancer 30:551-8 (2011)
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PMID:28664511
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The Role of Nitrosamine (NNK) in Breast Cancer Carcinogenesis.
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J Mammary Gland Biol Neoplasia 22:159-170 (2017)
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IKBKE is induced by STAT3 and tobacco carcinogen and determines chemosensitivity in non-small cell lung cancer.
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Oncogene 32:151-9 (2013)
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PMID:20106947
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Chen RJ, Ho YS, Guo HR, Wang YJ
  Title
Long-term nicotine exposure-induced chemoresistance is mediated by activation of Stat3 and downregulation of ERK1/2 via nAChR and beta-adrenoceptors in human bladder cancer cells.
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Toxicol Sci 115:118-30 (2010)
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PMID:20953833
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Lee CH, Chang YC, Chen CS, Tu SH, Wang YJ, Chen LC, Chang YJ, Wei PL, Chang HW, Chang CH, Huang CS, Wu CH, Ho YS
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Crosstalk between nicotine and estrogen-induced estrogen receptor activation induces alpha9-nicotinic acetylcholine receptor expression in human breast cancer cells.
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Breast Cancer Res Treat 129:331-45 (2011)
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PMID:29229539
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Bisphenol A (BPA) and cell signaling pathways.
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Biotechnol Adv 36:311-327 (2018)
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PMID:28251049
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Low-Dose Bisphenol A Exposure: A Seemingly Instigating Carcinogenic Effect on Breast Cancer.
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Carcinogenesis 38:252-260 (2017)
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Cancers (Basel) 12:E2440 (2020)
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J Mammary Gland Biol Neoplasia 20:39-50 (2015)
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Related
pathway
lve00980  Metabolism of xenobiotics by cytochrome P450
lve03320  PPAR signaling pathway
lve04010  MAPK signaling pathway
lve04024  cAMP signaling pathway
lve04150  mTOR signaling pathway
lve04151  PI3K-Akt signaling pathway
lve04370  VEGF signaling pathway
lve04915  Estrogen signaling pathway
lve05204  Chemical carcinogenesis - DNA adducts
lve05206  MicroRNAs in cancer
lve05208  Chemical carcinogenesis - reactive oxygen species
KO pathway
ko05207   
LinkDB

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