Head and neck squamous cell carcinoma (Homo sapiens)

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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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Ontology Terms

 

Bibliography

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  1. Casamayor A, Morrice NA, Alessi DR; ''Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo.''; Biochem J, 1999 PubMed Europe PMC Scholia
  2. 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
  3. ''''; https://clinicalgate.com/the-molecular-pathogenesis-of-head-and-neck-cancer/,
  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
  5. ''''; https://clinicalgate.com/the-molecular-pathogenesis-of-head-and-neck-cancer/.,
  6. 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
  7. Manning BD, Tee AR, Logsdon MN, Blenis J, Cantley LC; ''Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway.''; Mol Cell, 2002 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
142545view22:06, 16 March 2026Khanspersfixed typo
142512view02:34, 13 March 2026Khanspersupdated reference
142511view02:19, 13 March 2026Khansperswork in progress
142510view02:07, 13 March 2026Khansperswork in progress
142509view02:02, 13 March 2026Khanspersupdated lit refs, added LTBR and TNFR, removed GAB1 due to no reference
142508view00:55, 13 March 2026Khanspersincreased node sizes, converted interactions to graphical lines where appropriate, added WPID for Apoptosis, layout
141975view16:34, 28 November 2025EweitzClear deprecated metadata rendering
138027view22:35, 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
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

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AJUBAGeneProductENSG00000129474 (Ensembl)
AKT1GeneProductENSG00000142208 (Ensembl)
AKT2GeneProductENSG00000105221 (Ensembl)
AKT3GeneProductENSG00000117020 (Ensembl)
ApoptosisPathwayWP254 (WikiPathways)
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)
FGFR3GeneProductENSG00000068078 (Ensembl)
FKBP1AGeneProductENSG00000088832 (Ensembl)
HPV E6GeneProduct
HPV E7GeneProduct
HRASGeneProductENSG00000174775 (Ensembl)
IGF1RGeneProductENSG00000140443 (Ensembl)
IRF6GeneProductENSG00000117595 (Ensembl)
KEAP1GeneProductENSG00000079999 (Ensembl)
KRASGeneProductENSG00000133703 (Ensembl)
LTBRGeneProductLTBR (HGNC)
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)
TNFRGeneProductPF00020 (Pfam)
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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