Phosphoproteomic Analysis of Signaling Pathways in Head and Neck Squamous Cell Carcinoma Patient Samples
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 tumo...
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| Veröffentlicht in: | The American journal of pathology 2011-02, Vol.178 (2), p.548-571 |
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| creator | Frederick, Mitchell J VanMeter, Amy J Gadhikar, Mayur A Henderson, Ying C Yao, Hui Pickering, Curtis C Williams, Michelle D El-Naggar, Adel K Sandulache, Vlad Tarco, Emily Myers, Jeffrey N Clayman, Gary L Liotta, Lance A Petricoin, Emanuel F Calvert, Valerie S Fodale, Valentina Wang, Jing Weber, Randal S |
| description | 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. |
| doi_str_mv | 10.1016/j.ajpath.2010.10.044 |
| format | Article |
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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.</description><identifier>ISSN: 0002-9440</identifier><identifier>EISSN: 1525-2191</identifier><identifier>DOI: 10.1016/j.ajpath.2010.10.044</identifier><identifier>PMID: 21281788</identifier><identifier>CODEN: AJPAA4</identifier><language>eng</language><publisher>Bethesda, MD: Elsevier Inc</publisher><subject>Biological and medical sciences ; Biomarkers, Tumor - metabolism ; Blotting, Western ; Carcinoma, Squamous Cell - enzymology ; Carcinoma, Squamous Cell - metabolism ; Carcinoma, Squamous Cell - pathology ; Cell Line, Tumor ; Cluster Analysis ; Female ; Head and Neck Neoplasms - enzymology ; Head and Neck Neoplasms - metabolism ; Head and Neck Neoplasms - pathology ; Humans ; Immunohistochemistry ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical sciences ; Mucous Membrane - metabolism ; Mucous Membrane - pathology ; Neoplasm Proteins - metabolism ; Otorhinolaryngology (head neck, general aspects and miscellaneous) ; Otorhinolaryngology. Stomatology ; Pathology ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Phosphoproteins - metabolism ; Phosphorylation ; Protein Array Analysis ; Protein Kinase C - metabolism ; Proteomics - methods ; Regular ; Reproducibility of Results ; Signal Transduction ; Tumors</subject><ispartof>The American journal of pathology, 2011-02, Vol.178 (2), p.548-571</ispartof><rights>American Society for Investigative Pathology</rights><rights>2011 American Society for Investigative Pathology</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.</rights><rights>2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. 2011 American Society for Investigative Pathology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c613t-7ab7279b19631a00b316095a7d17e8a06e06011ab3f771ff0bc5322ba32ac5c73</citedby><cites>FETCH-LOGICAL-c613t-7ab7279b19631a00b316095a7d17e8a06e06011ab3f771ff0bc5322ba32ac5c73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3070553/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0002944010001409$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,3537,27901,27902,53766,53768,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24524101$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21281788$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Frederick, Mitchell J</creatorcontrib><creatorcontrib>VanMeter, Amy J</creatorcontrib><creatorcontrib>Gadhikar, Mayur A</creatorcontrib><creatorcontrib>Henderson, Ying C</creatorcontrib><creatorcontrib>Yao, Hui</creatorcontrib><creatorcontrib>Pickering, Curtis C</creatorcontrib><creatorcontrib>Williams, Michelle D</creatorcontrib><creatorcontrib>El-Naggar, Adel K</creatorcontrib><creatorcontrib>Sandulache, Vlad</creatorcontrib><creatorcontrib>Tarco, Emily</creatorcontrib><creatorcontrib>Myers, Jeffrey N</creatorcontrib><creatorcontrib>Clayman, Gary L</creatorcontrib><creatorcontrib>Liotta, Lance A</creatorcontrib><creatorcontrib>Petricoin, Emanuel F</creatorcontrib><creatorcontrib>Calvert, Valerie S</creatorcontrib><creatorcontrib>Fodale, Valentina</creatorcontrib><creatorcontrib>Wang, Jing</creatorcontrib><creatorcontrib>Weber, Randal S</creatorcontrib><title>Phosphoproteomic Analysis of Signaling Pathways in Head and Neck Squamous Cell Carcinoma Patient Samples</title><title>The American journal of pathology</title><addtitle>Am J Pathol</addtitle><description>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.</description><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Blotting, Western</subject><subject>Carcinoma, Squamous Cell - enzymology</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cluster Analysis</subject><subject>Female</subject><subject>Head and Neck Neoplasms - enzymology</subject><subject>Head and Neck Neoplasms - metabolism</subject><subject>Head and Neck Neoplasms - pathology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mucous Membrane - metabolism</subject><subject>Mucous Membrane - pathology</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Otorhinolaryngology (head neck, general aspects and miscellaneous)</subject><subject>Otorhinolaryngology. Stomatology</subject><subject>Pathology</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Phosphoproteins - metabolism</subject><subject>Phosphorylation</subject><subject>Protein Array Analysis</subject><subject>Protein Kinase C - metabolism</subject><subject>Proteomics - methods</subject><subject>Regular</subject><subject>Reproducibility of Results</subject><subject>Signal Transduction</subject><subject>Tumors</subject><issn>0002-9440</issn><issn>1525-2191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUsFu1DAQtRCILoU_QMgXxCnL2E7i5IJUrQpFqqDSwtmaOM7G2yRO7aRo_x6HXVrgwsn2-M17M_OGkNcM1gxY_n6_xv2IU7vm8Cu0hjR9QlYs41nCWcmekhUA8KRMUzgjL0LYx2cuCnhOzjjjBZNFsSLtTevC2LrRu8m43mp6MWB3CDZQ19Ct3cWXHXb0Jir9wEOgdqBXBmuKQ02_GH1Lt3cz9m4OdGO6jm7Qazu4HpcMa4aJbrEfOxNekmcNdsG8Op3n5PvHy2-bq-T666fPm4vrROdMTInESnJZVqzMBUOASrAcygxlzaQpEHIDOTCGlWikZE0Dlc4E5xUKjjrTUpyTD0feca56U-tYgsdOjd726A_KoVV__wy2VTt3rwRIyDIRCd6dCLy7m02YVG-Djr3hYGKbqkiLIo5cLFLpEam9C8Gb5kGFgVo8Unt19EgtHi3R6FFMe_NnhQ9Jv02JgLcnAAaNXeNx0DY84tKMp5H-sVUT53lvjVdBx5FrU1tv9KRqZ_9Xyb8EOppto-atOZiwd7OP9gfFVOAK1HbZp2WdWLywFErxExZex0w</recordid><startdate>20110201</startdate><enddate>20110201</enddate><creator>Frederick, Mitchell J</creator><creator>VanMeter, Amy J</creator><creator>Gadhikar, Mayur A</creator><creator>Henderson, Ying C</creator><creator>Yao, Hui</creator><creator>Pickering, Curtis C</creator><creator>Williams, Michelle D</creator><creator>El-Naggar, Adel K</creator><creator>Sandulache, Vlad</creator><creator>Tarco, Emily</creator><creator>Myers, Jeffrey N</creator><creator>Clayman, Gary L</creator><creator>Liotta, Lance A</creator><creator>Petricoin, Emanuel F</creator><creator>Calvert, Valerie S</creator><creator>Fodale, Valentina</creator><creator>Wang, Jing</creator><creator>Weber, Randal S</creator><general>Elsevier Inc</general><general>American Society for Investigative Pathology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110201</creationdate><title>Phosphoproteomic Analysis of Signaling Pathways in Head and Neck Squamous Cell Carcinoma Patient Samples</title><author>Frederick, Mitchell J ; VanMeter, Amy J ; Gadhikar, Mayur A ; Henderson, Ying C ; Yao, Hui ; Pickering, Curtis C ; Williams, Michelle D ; El-Naggar, Adel K ; Sandulache, Vlad ; Tarco, Emily ; Myers, Jeffrey N ; Clayman, Gary L ; Liotta, Lance A ; Petricoin, Emanuel F ; Calvert, Valerie S ; Fodale, Valentina ; Wang, Jing ; Weber, Randal S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c613t-7ab7279b19631a00b316095a7d17e8a06e06011ab3f771ff0bc5322ba32ac5c73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Biological and medical sciences</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Blotting, Western</topic><topic>Carcinoma, Squamous Cell - enzymology</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cluster Analysis</topic><topic>Female</topic><topic>Head and Neck Neoplasms - enzymology</topic><topic>Head and Neck Neoplasms - metabolism</topic><topic>Head and Neck Neoplasms - pathology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mucous Membrane - metabolism</topic><topic>Mucous Membrane - pathology</topic><topic>Neoplasm Proteins - metabolism</topic><topic>Otorhinolaryngology (head neck, general aspects and miscellaneous)</topic><topic>Otorhinolaryngology. 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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. 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| ispartof | The American journal of pathology, 2011-02, Vol.178 (2), p.548-571 |
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| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Biological and medical sciences Biomarkers, Tumor - metabolism Blotting, Western Carcinoma, Squamous Cell - enzymology Carcinoma, Squamous Cell - metabolism Carcinoma, Squamous Cell - pathology Cell Line, Tumor Cluster Analysis Female Head and Neck Neoplasms - enzymology Head and Neck Neoplasms - metabolism Head and Neck Neoplasms - pathology Humans Immunohistochemistry Investigative techniques, diagnostic techniques (general aspects) Male Medical sciences Mucous Membrane - metabolism Mucous Membrane - pathology Neoplasm Proteins - metabolism Otorhinolaryngology (head neck, general aspects and miscellaneous) Otorhinolaryngology. Stomatology Pathology Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Phosphoproteins - metabolism Phosphorylation Protein Array Analysis Protein Kinase C - metabolism Proteomics - methods Regular Reproducibility of Results Signal Transduction Tumors |
| title | Phosphoproteomic Analysis of Signaling Pathways in Head and Neck Squamous Cell Carcinoma Patient Samples |
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