Head and neck squamous cell carcinoma (Homo sapiens)

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ArcPathVisio Brace Ellipse EndoplasmicReticulum GolgiApparatus HexagonPathVisio MimDegradation Mitochondria Octagon PentagonPathVisio Rectangle RoundedRectangle SarcoplasmicReticulum TriangleEquilateralEast TrianglePathVisio none PAKT2PPAKT1PAKT3AKTCDKN1ACDK4CDK6NucleusSurvivalCell cycleProliferationInvasion and metastasisMultiple other targetsEIF4EApoptosisRB1MIRLET7CTP63MetforminAJUBAGAB1BIRC2CASP8NUMBHPV E6TERTFAT1FADDmTOR inhibitorsE2F1TP53IRF6MAML1PI3K inhibitorsMLST8PPMTORRPTOREGFRERBB2IGF1RFGFR2FGFR1FGFR3DDIT4SESN1SESN2PIK3R5PIK3CGFKBP1ARapamycinKEAP1CUL3SMAD4TGFBR2NOTCH1NOTCH2RICTORMAPKAP1MLST8PPMTORPTENPIP3PIK3R1PIK3R2PIK3CAPIK3CBPI3K class 1aNRASKRASHRASTSC1PPTSC2PRKAA1PRKAA2STK11RHEBPPRPS6CCND1HPV E7DifferentiationDifferentiationCSMD3VEGFAp14 ARF (CDKN2A)p16 INK4a(CDKN2A)LegendActivating mutationInactivating mutationRPS6KB2PPPPEIF4EBP1PDPK1CTNNB1NFE2L2Oxidative stressTRAF3CASP8RELANFKB1RELRELNFKB2InflammationAngiogenesisMigrationInflammationAngiogenesisMigrationmTORC2mTORC1Name: Head and neck squamous cell carcinomaOrganism: Homo sapiens


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](https://europepmc.org/articles/PMC4348071), [Fig 5 from Li et al](https://www.nature.com/articles/nature14129) and [Fig 33-3 from Clinicalgate](https://clinicalgate.com/the-molecular-pathogenesis-of-head-and-neck-cancer/).

Description is modified from [Iglesias-Bartolome et al](https://europepmc.org/articles/PMC4348071).

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

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Quality Tags

Image:Curated.pngApproved version
Image:Wplogo_31.pngCommunity: CPTAC
Image:MissingXref.pngAnnotate nodes

Ontology Terms

Pathway Ontology : cancer pathway disease pathway
 

Bibliography

  1. ''''; https://clinicalgate.com/the-molecular-pathogenesis-of-head-and-neck-cancer/,
  2. 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
  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. 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

History

View all...
CompareRevisionActionTimeUserComment
138027
Approved
view22:35, 11 March 2025EweitzStandardize case
138026view22:34, 11 March 2025EweitzEconomize layout
138025view22:31, 11 March 2025EweitzTailor node width
138024view22:30, 11 March 2025EweitzEconomize layout
138023view22:22, 11 March 2025EweitzEconomize layout
138020view13:01, 11 March 2025EweitzRefine state position
138019view13:00, 11 March 2025EweitzEconomize layout
138018view12:57, 11 March 2025EweitzEconomize layout
138007view04:04, 11 March 2025EweitzStandardize case
138006view04:03, 11 March 2025EweitzEconomize layout
138005view04:02, 11 March 2025EweitzStack nodes
138004view04:00, 11 March 2025EweitzEconomize layout
138003view03:58, 11 March 2025EweitzEconomize layout
138002view03:55, 11 March 2025EweitzEconomize layout
138001view03:51, 11 March 2025EweitzEconomize layout
138000view03:50, 11 March 2025EweitzTailor node height
137999view03:48, 11 March 2025EweitzEconomize layout
137083view21:59, 27 February 2025KhanspersModified description
129347
CPTAC
view09:25, 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

External references

DataNodes

View all...
Name  ↓Type  ↓Database reference  ↓Comment  ↓
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)
MetforminMetaboliteQ19484 (Wikidata)
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)
RapamycinMetaboliteCHEBI:9168 (ChEBI)
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)
p14 ARF (CDKN2A)GeneProductENSG00000147889 (Ensembl)
p16 INK4a (CDKN2A)GeneProductENSG00000147889 (Ensembl)

Annotated Interactions

No annotated interactions

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