title: The role of Pea3 group transcription factors in esophageal squamous cell carcinoma.
abstract: The transcription factors Pea3, Erm, and Er81 can promote cancer initiation and progression in various types of solid tumors. However, their role in esophageal squamous cell carcinoma (ESCC) has not been elucidated. In this study, we found that the expression levels of Pea3 and Erm, but not that of Er81, were significantly higher in ESCC compared with nontumor esophageal epithelium. A high level of Pea3 expression was significantly correlated with a shorter overall survival in a cohort of 81 patients with ESCC and the subgroup with N1 stage tumor (Wilcoxon-Gehan test, P = 0.016 and P = 0.001, respectively). Pea3 was overexpressed in seven ESCC cell lines compared with two immortalized esophageal cell lines. Pea3 knockdown reduced cell proliferation and suppressed nonadherent growth, migration, and invasion in ESCC cells in vitro. In addition, Pea3 knockdown in ESCC cells resulted in a down-regulation of phospho-Akt and matrix metalloproteinase 13, whereas a significant positive correlation in the expression levels was observed between Pea3 and phospho-Akt (r = 0.281, P < 0.013) and between Pea3 and matrix metalloproteinase 13 in the human specimens (r = 0.462, P < 0.001). Moreover, Pea3 modulated the sensitivity of EC109 cells to doxorubicin, probably via reduced activity of the phosphatidylinositol 3-kinase-Akt-mammalian target of Rapamycin complex 1 pathway on Pea3 knockdown. In conclusion, our results suggest that Pea3 plays an important role in the progression of ESCC.
authors.affiliation: Center for Cancer Research and Cell Biology, Queen's University of Belfast, Belfast, United Kingdom.
authors.forename: Hiu-Fung
authors.initials: HF
authors.lastname: Yuen
authors.forename: Cian M
authors.initials: CM
authors.lastname: McCrudden
authors.forename: Ka-Kui
authors.initials: KK
authors.lastname: Chan
authors.forename: Yuen-Piu
authors.initials: YP
authors.lastname: Chan
authors.forename: Michelle Lok-Yee
authors.initials: ML
authors.lastname: Wong
authors.forename: Kelvin Yuen-Kwong
authors.initials: KY
authors.lastname: Chan
authors.forename: Ui-Soon
authors.initials: US
authors.lastname: Khoo
authors.forename: Simon
authors.initials: S
authors.lastname: Law
authors.forename: Gopesh
authors.initials: G
authors.lastname: Srivastava
authors.forename: Terence R
authors.initials: TR
authors.lastname: Lappin
authors.forename: Kwok-Wah
authors.initials: KW
authors.lastname: Chan
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Tanani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C095239:ETV1 protein, human; C086680:ETV5 protein, human; D014157:Transcription Factors; C065788:transcription factor PEA3