title: Phosphoproteomic analysis of signaling pathways in head and neck squamous cell carcinoma patient samples.
abstract: Molecular targeted therapy represents a promising new strategy for treating cancers because many small-molecule inhibitors targeting protein kinases have recently become available. Reverse-phase protein microarrays (RPPAs) are a useful platform for identifying dysregulated signaling pathways in tumors and can provide insight into patient-specific differences. In the present study, RPPAs were used to examine 60 protein end points (predominantly phosphoproteins) in matched tumor and nonmalignant biopsy specimens from 23 patients with head and neck squamous cell carcinoma to characterize the cancer phosphoproteome. RPPA identified 18 of 60 analytes globally elevated in tumors versus healthy tissue and 17 of 60 analytes that were decreased. The most significantly elevated analytes in tumor were checkpoint kinase (Chk) 1 serine 345 (S345), Chk 2 S33/35, eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) S65, protein kinase C (PKC) ζ/ι threonine 410/412 (T410/T412), LKB1 S334, inhibitor of kappaB alpha (IκB-α) S32, eukaryotic translation initiation factor 4E (eIF4E) S209, Smad2 S465/67, insulin receptor substrate 1 (IRS-1) S612, mitogen-activated ERK kinase 1/2 (MEK1/2) S217/221, and total PKC ι. To our knowledge, this is the first report of elevated PKC ι in head and neck squamous cell carcinoma that may have significance because PKC ι is an oncogene in several other tumor types, including lung cancer. The feasibility of using RPPA for developing theranostic tests to guide personalized therapy is discussed in the context of these data.
authors.affiliation: Department of Head and Neck Surgery, University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA. mfrederi@mdanderson.org
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Frederick
authors.forename: Amy J
authors.initials: AJ
authors.lastname: VanMeter
authors.forename: Mayur A
authors.initials: MA
authors.lastname: Gadhikar
authors.forename: Ying C
authors.initials: YC
authors.lastname: Henderson
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.forename: Curtis C
authors.initials: CC
authors.lastname: Pickering
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Williams
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: Vlad
authors.initials: V
authors.lastname: Sandulache
authors.forename: Emily
authors.initials: E
authors.lastname: Tarco
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
authors.forename: Gary L
authors.initials: GL
authors.lastname: Clayman
authors.forename: Lance A
authors.initials: LA
authors.lastname: Liotta
authors.forename: Emanuel F
authors.initials: EF
authors.lastname: Petricoin
authors.forename: Valerie S
authors.initials: VS
authors.lastname: Calvert
authors.forename: Valentina
authors.initials: V
authors.lastname: Fodale
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Randal S
authors.initials: RS
authors.lastname: Weber
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D005260:Female; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D040081:Protein Array Analysis; D011493:Protein Kinase C / Q000378:metabolism; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D015398:Signal Transduction
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D011493:Protein Kinase C