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.ff8fb2f64c82RelAc-Relparentid=P31749; parentsymbol=AKT1; site=kDGAtMKtFCGtPEy; position=thr308; sitegrpid=447856; ptm=p; direction=uparentid=P31749; parentsymbol=AKT1; site=RPHFPQFsysAsGtA; position=ser473; sitegrpid=447855; ptm=p; direction=uparentid=P31751; parentsymbol=AKT2; site=sDGAtMKtFCGtPEy; position=thr309; sitegrpid=448537; ptm=p; direction=uparentid=Q9Y243; parentsymbol=AKT3; site=tDAATMKtFCGtPEy; position=thr305; sitegrpid=448521; ptm=p; direction=uparentid=P49815; parentsymbol=TSC2; site=GLRPRGytISDsAPs; position=thr1462; sitegrpid=448546; ptm=p; direction=dparentid=P49815; parentsymbol=TSC2; site=sFRARstsLNERPKs; position=ser939; sitegrpid=448501; ptm=p; direction=dparentid=P42345; parentsymbol=MTOR; site=RsRtRtDsysAGQsV; position=ser2448; sitegrpid=447578; ptm=p; direction=uparentid=P42345; parentsymbol=MTOR; site=tVPEsIHsFIGDGLV; position=ser2481; sitegrpid=447498; ptm=p; direction=uparentid=P62753; parentsymbol=RPS6; site=IAKRRRLssLRAsts; position=ser235; sitegrpid=448092; ptm=p; direction=uparentid=P62753; parentsymbol=RPS6; site=AKRRRLssLRAstsK; position=ser236; sitegrpid=448093; ptm=p; direction=uparentid=Q13541; parentsymbol=EIF4EBP1; site=FLMECrNsPVtktPP; position=ser65; sitegrpid=447527; ptm=p; direction=dparentid=Q13541; parentsymbol=EIF4EBP1; site=rNsPVtktPPRDLPt; position=thr70; sitegrpid=447528; ptm=p; direction=dparentid=Q13541; parentsymbol=EIF4EBP1; site=GGtLFsttPGGtRII; position=thr46; sitegrpid=447496; ptm=p; direction=dparentid=Q13541; parentsymbol=EIF4EBP1; site=PPGDysttPGGtLFs; position=thr37; sitegrpid=447497; ptm=p; direction=dparentid=P42345; parentsymbol=MTOR; site=tVPEsIHsFIGDGLV; position=ser2481; sitegrpid=447498; ptm=p; direction=uparentid=P42345; parentsymbol=MTOR; site=RsRtRtDsysAGQsV; position=ser2448; sitegrpid=447578; ptm=p; direction=uHPV6 inactivates TP53 in tumors without somatic TP53 mutationsf64fb2fb2fb2fb2fb2fb2cancer pathwayPW:0000605Pathway Ontology25514926PubMedPhosphoSitePlus, 2014: mutations, PTMs and recalibrations.Nucleic Acids Res2015Hornbeck PVZhang BMurray BKornhauser JMLatham VSkrzypek EPubMedhttps://clinicalgate.com/the-molecular-pathogenesis-of-head-and-neck-cancer/31695792PubMedComprehensive characterization of the alternative splicing landscape in head and neck squamous cell carcinoma reveals novel events associated with tumorigenesis and the immune microenvironment.Theranostics2019Li ZXZheng ZQWei ZHZhang LLLi FLin LLiu RQHuang XDLv JWChen FPHe XJGuan JLKou JMa JZhou GQSun Y23847349PubMedExploiting the head and neck cancer oncogenome: widespread PI3K-mTOR pathway alterations and novel molecular targets.Cancer Discov2013Iglesias-Bartolome RMartin DGutkind JSdisease pathwayPW:0000013Pathway Ontologyhead and neck carcinomaDOID:1542Disease