MUC20 overexpression predicts poor prognosis and enhances EGF-induced malignant phenotypes via activation of the EGFR-STAT3 pathway in endometrial cancer
Journal
Gynecologic Oncology
Journal Volume
128
Journal Issue
3
Pages
560-567
Date Issued
2013
Author(s)
Wang S.-W.
Chen C.-W.
Huang M.-R.
Huang H.-C.
Abstract
Objective Mucins play a critical role in the malignancy of various tumors and have been identified as diagnostic markers and as attractive therapeutic targets. However, the role of mucin (MUC) 20 in endometrial cancer (EC) is still unknown. Methods The relationship between MUC20 expression and clinical characteristics of EC was analyzed in 97 EC tumors and 16 normal tissues by immunohistochemistry. Effects of MUC20 on EC cells, HEC-1A and RL95-2, were examined by in vitro cell growth, migration, and invasion assays, as well as in vivo tumor growth in SCID mouse model. Western blotting was performed to analyze signaling pathways modulated by MUC20. Results MUC20 expression was significantly higher in EC tumors compared with the normal tissue. High levels of MUC20 expression in EC tumors were correlated with an unfavorable histologic subtype. Furthermore, MUC20 was an independent prognostic factor for poor survival as evaluated by multivariate analyses. Overexpression of MUC20 in EC cells significantly enhanced cell growth, migration, and invasion, as well as tumor growth in vivo. The MUC20-enhanced invasive behavior was significantly blocked by erlotinib, an EGFR inhibitor. Moreover, MUC20 overexpression enhanced EGF-mediated migration and invasion, suggesting a critical role of EGFR in MUC20-mediated effects. We found that MUC20 overexpression could enhance EGF-induced phosphorylation of EGFR and STAT3. Inhibition of the STAT3 activity by its inhibitor Stattic significantly suppressed the MUC20-enhanced invasive behavior. Conclusions MUC20 is novel prognostic factor for EC and its overexpression enhances EGF-triggered invasive behavior through activation of EGFR-STAT3 pathway. ? 2012 Elsevier Inc.
SDGs
Other Subjects
biological marker; epidermal growth factor receptor; erlotinib; glycoprotein; muc20 protein; STAT3 protein; unclassified drug; adult; animal experiment; animal model; article; cancer cell; cancer invasion; cancer prognosis; cancer survival; cell migration; controlled study; correlational study; endometrium cancer; enzyme activity; enzyme inhibition; female; histopathology; human; human tissue; in vivo study; major clinical study; mouse; nonhuman; phenotype; priority journal; protein expression; protein phosphorylation; SCID mouse; signal transduction; tumor growth; Western blotting; Animals; Cell Growth Processes; Cell Line, Tumor; Disease Models, Animal; Endometrial Neoplasms; Epidermal Growth Factor; Female; Humans; Mice; Mice, SCID; Middle Aged; Mucins; Neoplasm Staging; Phenotype; Phosphorylation; Prognosis; Receptor, Epidermal Growth Factor; Signal Transduction; STAT3 Transcription Factor; Transfection
Type
journal article