Interaction of Snail and p38 mitogen-activated protein kinase results in shorter overall survival of ovarian cancer patients.
Epithelial ovarian cancer is a highly metastatic disease and the leading cause of death among cancer of the female genital tract. Abnormal epidermal growth factor receptor (EGFR) signalling has been shown to be involved in epithelial-mesenchymal transition (EMT), an early step during metastasis. Additionally, over-expression of the E-cadherin repressor Snail, a key regulator of EMT, has previously been found to be associated with unfavourable prognostic features. Thus, the aim of our study was to elucidate the role of EGFR-dependent signalling pathways for Snail expression in ovarian cancer. For this purpose, we analysed 25 formalin-fixed and paraffin-embedded (FFPE) primary tumours and their corresponding metastases for the expression of 25 signalling pathway molecules by reverse phase protein arrays. We found a significant correlation of Snail with EGFR((Tyr1086)) and p38 MAPK((Thr180/Tyr182)) in primary ovarian carcinoma and with EGFR((Tyr1086)) in their corresponding metastasis. Additionally, we showed that high expression levels of Snail in primary tumours combined with high expression levels of the phosphorylated p38 MAPK((Thr180/Tyr182)) in metastasis lead to an increased risk for death in ovarian carcinoma patients. Thus, for future combinatorial cancer therapy, drug combinations that best target the deregulated protein network in each individual patient should be selected.
Hipp
Susanne
S
Institut für Pathologie, Technische Universität München, Trogerstrasse 18, 81675, Munich, Germany.
Berg
Daniela
D
Ergin
Bilge
B
Schuster
Tibor
T
Hapfelmeier
Alexander
A
Walch
Axel
A
Avril
Stefanie
S
Schmalfeldt
Barbara
B
Höfler
Heinz
H
Becker
Karl-Friedrich
KF
D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000378:metabolism* / Q000401:mortality*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality*; D011379:Prognosis; D012189:Retrospective Studies; D015398:Signal Transduction / Q000502:physiology; D000071250:Snail Family Transcription Factors; D015996:Survival Rate; D014157:Transcription Factors / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases