Head and neck squamous cell carcinoma (WP4674)

Homo sapiens

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 [https://europepmc.org/articles/PMC4348071 Fig 1 from Iglesias-Bartolome et al], [https://www.nature.com/articles/nature14129 Fig 5 from Li et al] and [https://clinicalgate.com/the-molecular-pathogenesis-of-head-and-neck-cancer/ Fig 33-3 from Clinicalgate]. Description is modified from [https://europepmc.org/articles/PMC4348071 Iglesias-Bartolome et al]. Protein phosphorylation sites were added based on information from PhosphoSitePlus (R), www.phosphosite.org.


Kristina Hanspers , Egon Willighagen , Denise Slenter , Marvin Martens , and Eric Weitz


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Homo sapiens


CPTAC Diseases


Disease Ontology

head and neck carcinoma


Label Type Compact URI Comment
metformin Metabolite wikidata:Q19484
rapamycin Metabolite chebi:9168
mTOR inhibitors Metabolite chebi:68481
PI3K inhibitors Metabolite chebi:50914
PIP3 Metabolite chebi:16618
FKBP1A GeneProduct ensembl:ENSG00000088832
DDIT4 GeneProduct ensembl:ENSG00000168209
SMAD4 GeneProduct ensembl:ENSG00000141646
KEAP1 GeneProduct ensembl:ENSG00000079999
EIF4E GeneProduct ensembl:ENSG00000151247
RB1 GeneProduct ensembl:ENSG00000139687
MIRLET7C GeneProduct ensembl:ENSG00000199030
TP63 GeneProduct ensembl:ENSG00000073282
AJUBA GeneProduct ensembl:ENSG00000129474
GAB1 GeneProduct ensembl:ENSG00000109458
RICTOR GeneProduct ensembl:ENSG00000164327
MLST8 GeneProduct ensembl:ENSG00000167965
PIK3R5 GeneProduct ensembl:ENSG00000141506
BIRC2 GeneProduct ensembl:ENSG00000110330
CASP8 GeneProduct ensembl:ENSG00000064012
NUMB GeneProduct ensembl:ENSG00000133961
TERT GeneProduct ensembl:ENSG00000164362
CDKN1A GeneProduct ensembl:ENSG00000124762
NOTCH1 GeneProduct ensembl:ENSG00000148400
FAT1 GeneProduct ensembl:ENSG00000083857
FADD GeneProduct ensembl:ENSG00000168040
E2F1 GeneProduct ensembl:ENSG00000101412
PIK3CG GeneProduct ensembl:ENSG00000105851
MAPKAP1 GeneProduct ensembl:ENSG00000119487
TP53 GeneProduct ensembl:ENSG00000141510
IRF6 GeneProduct ensembl:ENSG00000117595
MAML1 GeneProduct ensembl:ENSG00000161021
EGFR GeneProduct ensembl:ENSG00000146648
PTEN GeneProduct ensembl:ENSG00000171862
AKT1 GeneProduct ensembl:ENSG00000142208
PIK3R1 GeneProduct ensembl:ENSG00000145675
PIK3R2 GeneProduct ensembl:ENSG00000105647
PIK3CA GeneProduct ensembl:ENSG00000121879
PIK3CB GeneProduct ensembl:ENSG00000051382
AKT2 GeneProduct ensembl:ENSG00000105221
AKT3 GeneProduct ensembl:ENSG00000117020
NRAS GeneProduct ensembl:ENSG00000213281
KRAS GeneProduct ensembl:ENSG00000133703
HRAS GeneProduct ensembl:ENSG00000174775
TSC1 GeneProduct ensembl:ENSG00000165699
TSC2 GeneProduct ensembl:ENSG00000103197
PRKAA1 GeneProduct ensembl:ENSG00000132356
PRKAA2 GeneProduct ensembl:ENSG00000162409
STK11 GeneProduct ensembl:ENSG00000118046
RHEB GeneProduct ensembl:ENSG00000106615
MTOR GeneProduct ensembl:ENSG00000198793
RPTOR GeneProduct ensembl:ENSG00000141564
MLST8 GeneProduct ensembl:ENSG00000167965
RPS6 GeneProduct ensembl:ENSG00000137154
SESN1 GeneProduct ensembl:ENSG00000080546
SESN2 GeneProduct ensembl:ENSG00000130766
CCND1 GeneProduct ensembl:ENSG00000110092
NOTCH2 GeneProduct ensembl:ENSG00000134250
CDK4 GeneProduct ensembl:ENSG00000135446
CDK6 GeneProduct ensembl:ENSG00000105810
TGFBR2 GeneProduct ensembl:ENSG00000163513
CSMD3 GeneProduct ensembl:ENSG00000164796
VEGFA GeneProduct ensembl:ENSG00000112715
p14 ARF (CDKN2A) GeneProduct ensembl:ENSG00000147889
p16 INK4a(CDKN2A) GeneProduct ensembl:ENSG00000147889
RPS6KB2 GeneProduct ncbigene:6199
EIF4EBP1 GeneProduct ncbigene:1978
PDPK1 GeneProduct ensembl:ENSG00000140992
MTOR GeneProduct ensembl:ENSG00000198793
CTNNB1 GeneProduct ensembl:ENSG00000168036
CUL3 GeneProduct ensembl:ENSG00000036257
NFE2L2 GeneProduct ensembl:ENSG00000116044
ERBB2 GeneProduct ncbigene:2064
IGF1R GeneProduct ensembl:ENSG00000140443
FGFR2 GeneProduct ensembl:ENSG00000066468
FGFR1 GeneProduct ensembl:ENSG00000077782
FGFR3 GeneProduct ensembl:ENSG00000068078
TRAF3 GeneProduct ensembl:ENSG00000131323
CASP8 GeneProduct ensembl:ENSG00000064012
RELA GeneProduct ensembl:ENSG00000173039 RelA
NFKB1 GeneProduct ensembl:ENSG00000109320
REL GeneProduct ensembl:ENSG00000162924 c-Rel
REL GeneProduct ensembl:ENSG00000162924
NFKB2 GeneProduct ensembl:ENSG00000077150


  1. Exploiting the head and neck cancer oncogenome: widespread PI3K-mTOR pathway alterations and novel molecular targets. Iglesias-Bartolome R, Martin D, Gutkind JS. Cancer Discov. 2013 Jul;3(7):722–5. PubMed Europe PMC Scholia
  2. PhosphoSitePlus, 2014: mutations, PTMs and recalibrations. Hornbeck PV, Zhang B, Murray B, Kornhauser JM, Latham V, Skrzypek E. Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20. PubMed Europe PMC Scholia
  3. Comprehensive characterization of the alternative splicing landscape in head and neck squamous cell carcinoma reveals novel events associated with tumorigenesis and the immune microenvironment. Li ZX, Zheng ZQ, Wei ZH, Zhang LL, Li F, Lin L, et al. Theranostics. 2019 Oct 14;9(25):7648–65. PubMed Europe PMC Scholia