Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma

Janine G. Einspahr, Valerie Calvert, David S. Alberts, Clara Curiel-Lewandrowski, James Warneke, Robert Krouse, Steven P. Stratton, Lance Liotta, Caterina Longo, Giovanni Pellicani, Anil Prasad, Paul Sagerman, Yira Bermudez, Jianghong Deng, G. Timothy Bowden, Emanuel F. Petricoin

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Reverse phase protein microarray analysis was used to identify cell signaling derangements in squamous cell carcinoma (SCC) compared with actinic keratosis (AK) and upper inner arm (UIA). We analyzed two independent tissue sets with isolation and enrichment of epithelial cells by laser capture microdissection. Set 1 served as a pilot and a means to identify protein pathway activation alterations that could be further validated in a second independent set. Set 1 was comprised of 4 AK, 13 SCC, and 20 UIA. Set 2 included 15 AK, 9 SCCs, and 20 UIAs. Activation of 51 signaling proteins, known to be involved in tumorigenesis, were assessed for set 1 and showed that the MEK-ERK [mitogen-activated protein (MAP)/extracellular signalregulated (ERK; MEK)] pathway was activated in SCC compared with AK and UIA, and that epidermal growth factor receptor (EGFR) and mTOR pathways were aberrantly activated in SCC. Unsupervised twoway hierarchical clustering revealed that AK and UIA shared a common signaling network activation architecture while SCC was dramatically different. Statistical analysis found that prosurvival signaling through phosphorylation of ASK and 4EBP1 as well as increased Bax and Bak expression was higher in AK compared with UIA. We expanded pathway network activation mapping in set 2 to 101 key signaling proteins, which corroborated activation of MEK-ERK, EGFR, and mTOR pathways through discovery of a number of upstream and downstream signaling molecules within these pathways to conclude that SCC is indeed a pathway activation-driven disease. Pathway activation mapping of SCC compared with AK revealed several interconnected networks that could be targeted with drug therapy for potential chemoprevention and therapeutic applications.

Original languageEnglish
Pages (from-to)403-413
Number of pages11
JournalCancer Prevention Research
Volume5
Issue number3
DOIs
Publication statusPublished - Mar 2012

Fingerprint

Actinic Keratosis
Squamous Cell Carcinoma
Skin
Arm
Proteins
Mitogen-Activated Protein Kinase Kinases
Epidermal Growth Factor Receptor
Laser Capture Microdissection
Protein Array Analysis
MAP Kinase Signaling System
Chemoprevention
Mitogens
Cluster Analysis
Carcinogenesis
Epithelial Cells
Phosphorylation
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Einspahr, J. G., Calvert, V., Alberts, D. S., Curiel-Lewandrowski, C., Warneke, J., Krouse, R., ... Petricoin, E. F. (2012). Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma. Cancer Prevention Research, 5(3), 403-413. https://doi.org/10.1158/1940-6207.CAPR-11-0427

Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma. / Einspahr, Janine G.; Calvert, Valerie; Alberts, David S.; Curiel-Lewandrowski, Clara; Warneke, James; Krouse, Robert; Stratton, Steven P.; Liotta, Lance; Longo, Caterina; Pellicani, Giovanni; Prasad, Anil; Sagerman, Paul; Bermudez, Yira; Deng, Jianghong; Bowden, G. Timothy; Petricoin, Emanuel F.

In: Cancer Prevention Research, Vol. 5, No. 3, 03.2012, p. 403-413.

Research output: Contribution to journalArticle

Einspahr, JG, Calvert, V, Alberts, DS, Curiel-Lewandrowski, C, Warneke, J, Krouse, R, Stratton, SP, Liotta, L, Longo, C, Pellicani, G, Prasad, A, Sagerman, P, Bermudez, Y, Deng, J, Bowden, GT & Petricoin, EF 2012, 'Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma', Cancer Prevention Research, vol. 5, no. 3, pp. 403-413. https://doi.org/10.1158/1940-6207.CAPR-11-0427
Einspahr, Janine G. ; Calvert, Valerie ; Alberts, David S. ; Curiel-Lewandrowski, Clara ; Warneke, James ; Krouse, Robert ; Stratton, Steven P. ; Liotta, Lance ; Longo, Caterina ; Pellicani, Giovanni ; Prasad, Anil ; Sagerman, Paul ; Bermudez, Yira ; Deng, Jianghong ; Bowden, G. Timothy ; Petricoin, Emanuel F. / Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma. In: Cancer Prevention Research. 2012 ; Vol. 5, No. 3. pp. 403-413.
@article{728743bf38b94edf89588662633c1abd,
title = "Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma",
abstract = "Reverse phase protein microarray analysis was used to identify cell signaling derangements in squamous cell carcinoma (SCC) compared with actinic keratosis (AK) and upper inner arm (UIA). We analyzed two independent tissue sets with isolation and enrichment of epithelial cells by laser capture microdissection. Set 1 served as a pilot and a means to identify protein pathway activation alterations that could be further validated in a second independent set. Set 1 was comprised of 4 AK, 13 SCC, and 20 UIA. Set 2 included 15 AK, 9 SCCs, and 20 UIAs. Activation of 51 signaling proteins, known to be involved in tumorigenesis, were assessed for set 1 and showed that the MEK-ERK [mitogen-activated protein (MAP)/extracellular signalregulated (ERK; MEK)] pathway was activated in SCC compared with AK and UIA, and that epidermal growth factor receptor (EGFR) and mTOR pathways were aberrantly activated in SCC. Unsupervised twoway hierarchical clustering revealed that AK and UIA shared a common signaling network activation architecture while SCC was dramatically different. Statistical analysis found that prosurvival signaling through phosphorylation of ASK and 4EBP1 as well as increased Bax and Bak expression was higher in AK compared with UIA. We expanded pathway network activation mapping in set 2 to 101 key signaling proteins, which corroborated activation of MEK-ERK, EGFR, and mTOR pathways through discovery of a number of upstream and downstream signaling molecules within these pathways to conclude that SCC is indeed a pathway activation-driven disease. Pathway activation mapping of SCC compared with AK revealed several interconnected networks that could be targeted with drug therapy for potential chemoprevention and therapeutic applications.",
author = "Einspahr, {Janine G.} and Valerie Calvert and Alberts, {David S.} and Clara Curiel-Lewandrowski and James Warneke and Robert Krouse and Stratton, {Steven P.} and Lance Liotta and Caterina Longo and Giovanni Pellicani and Anil Prasad and Paul Sagerman and Yira Bermudez and Jianghong Deng and Bowden, {G. Timothy} and Petricoin, {Emanuel F.}",
year = "2012",
month = "3",
doi = "10.1158/1940-6207.CAPR-11-0427",
language = "English",
volume = "5",
pages = "403--413",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

TY - JOUR

T1 - Functional protein pathway activation mapping of the progression of normal skin to squamous cell carcinoma

AU - Einspahr, Janine G.

AU - Calvert, Valerie

AU - Alberts, David S.

AU - Curiel-Lewandrowski, Clara

AU - Warneke, James

AU - Krouse, Robert

AU - Stratton, Steven P.

AU - Liotta, Lance

AU - Longo, Caterina

AU - Pellicani, Giovanni

AU - Prasad, Anil

AU - Sagerman, Paul

AU - Bermudez, Yira

AU - Deng, Jianghong

AU - Bowden, G. Timothy

AU - Petricoin, Emanuel F.

PY - 2012/3

Y1 - 2012/3

N2 - Reverse phase protein microarray analysis was used to identify cell signaling derangements in squamous cell carcinoma (SCC) compared with actinic keratosis (AK) and upper inner arm (UIA). We analyzed two independent tissue sets with isolation and enrichment of epithelial cells by laser capture microdissection. Set 1 served as a pilot and a means to identify protein pathway activation alterations that could be further validated in a second independent set. Set 1 was comprised of 4 AK, 13 SCC, and 20 UIA. Set 2 included 15 AK, 9 SCCs, and 20 UIAs. Activation of 51 signaling proteins, known to be involved in tumorigenesis, were assessed for set 1 and showed that the MEK-ERK [mitogen-activated protein (MAP)/extracellular signalregulated (ERK; MEK)] pathway was activated in SCC compared with AK and UIA, and that epidermal growth factor receptor (EGFR) and mTOR pathways were aberrantly activated in SCC. Unsupervised twoway hierarchical clustering revealed that AK and UIA shared a common signaling network activation architecture while SCC was dramatically different. Statistical analysis found that prosurvival signaling through phosphorylation of ASK and 4EBP1 as well as increased Bax and Bak expression was higher in AK compared with UIA. We expanded pathway network activation mapping in set 2 to 101 key signaling proteins, which corroborated activation of MEK-ERK, EGFR, and mTOR pathways through discovery of a number of upstream and downstream signaling molecules within these pathways to conclude that SCC is indeed a pathway activation-driven disease. Pathway activation mapping of SCC compared with AK revealed several interconnected networks that could be targeted with drug therapy for potential chemoprevention and therapeutic applications.

AB - Reverse phase protein microarray analysis was used to identify cell signaling derangements in squamous cell carcinoma (SCC) compared with actinic keratosis (AK) and upper inner arm (UIA). We analyzed two independent tissue sets with isolation and enrichment of epithelial cells by laser capture microdissection. Set 1 served as a pilot and a means to identify protein pathway activation alterations that could be further validated in a second independent set. Set 1 was comprised of 4 AK, 13 SCC, and 20 UIA. Set 2 included 15 AK, 9 SCCs, and 20 UIAs. Activation of 51 signaling proteins, known to be involved in tumorigenesis, were assessed for set 1 and showed that the MEK-ERK [mitogen-activated protein (MAP)/extracellular signalregulated (ERK; MEK)] pathway was activated in SCC compared with AK and UIA, and that epidermal growth factor receptor (EGFR) and mTOR pathways were aberrantly activated in SCC. Unsupervised twoway hierarchical clustering revealed that AK and UIA shared a common signaling network activation architecture while SCC was dramatically different. Statistical analysis found that prosurvival signaling through phosphorylation of ASK and 4EBP1 as well as increased Bax and Bak expression was higher in AK compared with UIA. We expanded pathway network activation mapping in set 2 to 101 key signaling proteins, which corroborated activation of MEK-ERK, EGFR, and mTOR pathways through discovery of a number of upstream and downstream signaling molecules within these pathways to conclude that SCC is indeed a pathway activation-driven disease. Pathway activation mapping of SCC compared with AK revealed several interconnected networks that could be targeted with drug therapy for potential chemoprevention and therapeutic applications.

UR - http://www.scopus.com/inward/record.url?scp=84859447655&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859447655&partnerID=8YFLogxK

U2 - 10.1158/1940-6207.CAPR-11-0427

DO - 10.1158/1940-6207.CAPR-11-0427

M3 - Article

VL - 5

SP - 403

EP - 413

JO - Cancer Prevention Research

JF - Cancer Prevention Research

SN - 1940-6207

IS - 3

ER -