Head and neck squamous cell carcinoma (Homo sapiens)

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1-43233333NucleusSurvivalProliferationInvasion and MetastasisMultiple other targetsmTORC1Cell cycleEIF4ETERTIRF6mTOR inhibitorsKEAP1CDKN1AGAB1RB1FKBP1AMAML1BIRC2rapamycinPIK3R5AJUBAApoptosisFAT1PIK3CGDDIT4HPV E6CASP8NUMBMLST8E2F1FADDSMAD4MAPKAP1EGFRMIRLET7CTP63TP53NOTCH1metforminPI3K inhibitorsRICTORPTENAKT1PPPIP3PIK3R1PIK3R2PIK3CAPIK3CBAKT2PAKT3PNRASKRASHRASTSC1TSC2PPRKAA1PPRKAA2STK11RHEBMTORRPTORPPMLST8mTORC2RPS6PPSESN1SESN2CCND1HPV E7DifferentiationNOTCH2DifferentiationCDK4CDK6TGFBR2CSMD3VEGFAp14 ARF (CDKN2A)p16 INK4a(CDKN2A)LegendActivating mutationInactivating mutationRPS6KB2EIF4EBP1PPPPPDPK1MTORPPCTNNB1CUL3NFE2L2Oxidative stressERBB2IGF1RFGFR2FGFR1FGFR3TRAF3CASP8RELANFKB1RELRELNFKB2InflammationAngiogenesisMigrationInflammationAngiogenesisMigration


Description

HNSCC, which includes malignant squamous lesions arising in the oral cavity, larynx and pharynx, is the seventh most common cancer in the world.

HNSCC has a remarkable multiplicity and diversity of genetic alterations. Most genomic alterations in HNSCC converge in a handful of molecular pathways resulting in cell cycle deregulation, genomic instability, cell differentiation defects, and persistent mitogenic signaling, the latter involving aberrant PI3K/mTOR pathway activation thereby rendering HNSCC responsive to PI3K/mTOR inhibitors.

Pathway is based on Fig 1 from Iglesias-Bartolome et al, Fig 5 from Li et al and Fig 33-3 from Clinicalgate.

Description is modified from Iglesias-Bartolome et al.

Protein phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.

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Quality Tags

Ontology Terms

 

Bibliography

  1. Iglesias-Bartolome R, Martin D, Gutkind JS; ''Exploiting the head and neck cancer oncogenome: widespread PI3K-mTOR pathway alterations and novel molecular targets.''; Cancer Discov, 2013 PubMed Europe PMC Scholia
  2. ''''; https://clinicalgate.com/the-molecular-pathogenesis-of-head-and-neck-cancer/,
  3. Li ZX, Zheng ZQ, Wei ZH, Zhang LL, Li F, Lin L, Liu RQ, Huang XD, Lv JW, Chen FP, He XJ, Guan JL, Kou J, Ma J, Zhou GQ, Sun Y; ''Comprehensive characterization of the alternative splicing landscape in head and neck squamous cell carcinoma reveals novel events associated with tumorigenesis and the immune microenvironment.''; Theranostics, 2019 PubMed Europe PMC Scholia
  4. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E; ''PhosphoSitePlus, 2014: mutations, PTMs and recalibrations.''; Nucleic Acids Res, 2015 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
129347view09:25, 27 March 2024MkutmonOntology Term : 'cancer pathway' added !
129346view09:24, 27 March 2024MkutmonOntology Term : 'disease pathway' added !
127252view17:42, 28 August 2023KhanspersAdded literature reference and updated descriptions
123494view04:55, 29 July 2022EgonwMade a pathway clickable
117748view12:47, 22 May 2021EweitzModified title
112164view18:31, 29 September 2020Khanspersfixed ptm state comments
110867view05:13, 16 June 2020KhanspersModified description
110028view16:43, 13 April 2020KhanspersModified description
110027view16:41, 13 April 2020Khanspersfixed unconnected
109135view06:51, 18 February 2020KhanspersModified description
109134view06:48, 18 February 2020Khansperscleaned up lit refs
109133view06:47, 18 February 2020Khansperscleanup
109132view06:39, 18 February 2020Khanspersadded more content and cleaned up
109122view02:08, 18 February 2020Khanspersmore from TCGA paper
109121view01:40, 18 February 2020KhanspersAdded content from TCGA paper
108886view23:01, 4 February 2020KhanspersAdded more phospho sites
108885view22:43, 4 February 2020Khanspersadditional phosphosites
108884view22:17, 4 February 2020Khanspersadded phosphosites
108883view20:00, 4 February 2020KhanspersAdded phospho sites for TSC2 and MTOR
108830view00:19, 1 February 2020Khanspersupdated phosphosites
107474view23:12, 10 October 2019KhanspersModified description
107473view23:09, 10 October 2019Khanspersupdated content
107182view14:27, 17 September 2019MaintBotChEBI identifier normalization
106612view13:07, 11 September 2019Marvin M2Ontology Term : 'head and neck carcinoma' added !
106315view19:35, 20 August 2019Khanspersupdated interactions
106314view19:06, 20 August 2019Khanspersupdated CDKN2A
105371view15:17, 5 August 2019DeSlUpdated second title field for website link (since it wasn't visualised on page)
105370view15:15, 5 August 2019DeSlAdded title for website link.
105369view15:12, 5 August 2019DeSlConnected unconnected lines
105358view07:42, 4 August 2019EgonwTwo gene-gene interactions that are not mim-conversion.
105339view21:30, 1 August 2019KhanspersAdded Ras/Raf arm
105338view21:24, 1 August 2019KhanspersAdded GAB1, updated layout, changed title
105337view21:01, 1 August 2019Khanspersremoved erroneous lit refs
105336view20:50, 1 August 2019KhanspersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AJUBAGeneProductENSG00000129474 (Ensembl)
AKT1GeneProductENSG00000142208 (Ensembl)
AKT2GeneProductENSG00000105221 (Ensembl)
AKT3GeneProductENSG00000117020 (Ensembl)
ApoptosisPathway
BIRC2GeneProductENSG00000110330 (Ensembl)
CASP8GeneProductENSG00000064012 (Ensembl)
CCND1GeneProductENSG00000110092 (Ensembl)
CDK4GeneProductENSG00000135446 (Ensembl)
CDK6GeneProductENSG00000105810 (Ensembl)
CDKN1AGeneProductENSG00000124762 (Ensembl)
CSMD3GeneProductENSG00000164796 (Ensembl)
CTNNB1GeneProductENSG00000168036 (Ensembl)
CUL3GeneProductENSG00000036257 (Ensembl)
Cell cyclePathwayWP179 (WikiPathways)
DDIT4GeneProductENSG00000168209 (Ensembl)
E2F1GeneProductENSG00000101412 (Ensembl)
EGFRGeneProductENSG00000146648 (Ensembl)
EIF4EBP1GeneProduct1978 (Entrez Gene)
EIF4EGeneProductENSG00000151247 (Ensembl)
ERBB2GeneProduct2064 (Entrez Gene)
FADDGeneProductENSG00000168040 (Ensembl)
FAT1GeneProductENSG00000083857 (Ensembl)
FGFR1GeneProductENSG00000077782 (Ensembl)
FGFR2GeneProductENSG00000066468 (Ensembl)
FGFR3GeneProductENSG00000068078 (Ensembl)
FKBP1AGeneProductENSG00000088832 (Ensembl)
GAB1GeneProductENSG00000109458 (Ensembl)
HPV E6GeneProduct
HPV E7GeneProduct
HRASGeneProductENSG00000174775 (Ensembl)
IGF1RGeneProductENSG00000140443 (Ensembl)
IRF6GeneProductENSG00000117595 (Ensembl)
KEAP1GeneProductENSG00000079999 (Ensembl)
KRASGeneProductENSG00000133703 (Ensembl)
MAML1GeneProductENSG00000161021 (Ensembl)
MAPKAP1GeneProductENSG00000119487 (Ensembl)
MIRLET7CGeneProductENSG00000199030 (Ensembl)
MLST8GeneProductENSG00000167965 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
NFE2L2GeneProductENSG00000116044 (Ensembl)
NFKB1GeneProductENSG00000109320 (Ensembl)
NFKB2GeneProductENSG00000077150 (Ensembl)
NOTCH1GeneProductENSG00000148400 (Ensembl)
NOTCH2GeneProductENSG00000134250 (Ensembl)
NRASGeneProductENSG00000213281 (Ensembl)
NUMBGeneProductENSG00000133961 (Ensembl)
PDPK1GeneProductENSG00000140992 (Ensembl)
PI3K inhibitorsMetaboliteCHEBI:50914 (ChEBI)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PIK3CBGeneProductENSG00000051382 (Ensembl)
PIK3CGGeneProductENSG00000105851 (Ensembl)
PIK3R1GeneProductENSG00000145675 (Ensembl)
PIK3R2GeneProductENSG00000105647 (Ensembl)
PIK3R5GeneProductENSG00000141506 (Ensembl)
PIP3MetaboliteCHEBI:16618 (ChEBI)
PRKAA1GeneProductENSG00000132356 (Ensembl)
PRKAA2GeneProductENSG00000162409 (Ensembl)
PTENGeneProductENSG00000171862 (Ensembl)
RB1GeneProductENSG00000139687 (Ensembl)
RELAGeneProductENSG00000173039 (Ensembl) RelA
RELGeneProductENSG00000162924 (Ensembl)
RHEBGeneProductENSG00000106615 (Ensembl)
RICTORGeneProductENSG00000164327 (Ensembl)
RPS6GeneProductENSG00000137154 (Ensembl)
RPS6KB2GeneProduct6199 (Entrez Gene)
RPTORGeneProductENSG00000141564 (Ensembl)
SESN1GeneProductENSG00000080546 (Ensembl)
SESN2GeneProductENSG00000130766 (Ensembl)
SMAD4GeneProductENSG00000141646 (Ensembl)
STK11GeneProductENSG00000118046 (Ensembl)
TERTGeneProductENSG00000164362 (Ensembl)
TGFBR2GeneProductENSG00000163513 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
TP63GeneProductENSG00000073282 (Ensembl)
TRAF3GeneProductENSG00000131323 (Ensembl)
TSC1GeneProductENSG00000165699 (Ensembl)
TSC2GeneProductENSG00000103197 (Ensembl)
VEGFAGeneProductENSG00000112715 (Ensembl)
mTOR inhibitorsMetaboliteCHEBI:68481 (ChEBI)
metforminMetaboliteQ19484 (Wikidata)
p14 ARF (CDKN2A)GeneProductENSG00000147889 (Ensembl)
p16 INK4a (CDKN2A)GeneProductENSG00000147889 (Ensembl)
rapamycinMetaboliteCHEBI:9168 (ChEBI)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP4674"
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