Wilms' tumor 1 and signal transducers and activators of transcription 3 synergistically promote cell proliferation: a possible mechanism in sporadic Wilms' tumor.
Transcription factor Wilms' tumor 1 (WT1) was originally identified as a tumor suppressor for Wilms' tumor, but it is also overexpressed in a variety of cancer cells, suggesting a potential oncogenic function of WT1. It is important to understand molecular mechanisms underlying these dual functions of WT1 in tumorigenesis. In the current study, we report a synergistic role for signal transducers and activators of transcription 3 (STAT3) and WT1 in tumor development, including Wilms' tumor. STAT3 interacts with WT1 through its conserved domains both in vitro and in vivo. When STAT3 is activated, expression of WT1 enhances STAT3 transcriptional activity. Overexpression of WT1 and STAT3CA in NIH 3T3 increases the expression level of STAT3 target genes, including cyclin D1 and Bcl-xL, which results in an advantage of cell proliferation. Our results suggest that in the presence of activated STAT3, WT1 promotes cell proliferation instead of suppressing cell proliferation. Strikingly, STAT3 translocates to the nucleus and interacts with WT1 in a variety of primary Wilms' tumor cells, raising the hypothesis that WT1 and activated STAT3 in Wilms' tumor accelerate tumorigenesis.
Rong
Yu
Y
Department of Biological Sciences and Biotechnology and Institute of Biomedicine, Tsinghua University, Beijing 10084, China.
Cheng
Long
L
Ning
Hongxiu
H
Zou
Jizhen
J
Zhang
Yuanjiang
Y
Xu
Fang
F
Liu
Li
L
Chang
Zhijie
Z
Fu
Xin-Yuan
XY
D051700:Activating Transcription Factor 3 / Q000235:genetics*; D000818:Animals; D006528:Carcinoma, Hepatocellular; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D045744:Cell Line, Tumor; D004357:Drug Synergism; D006801:Humans; D007668:Kidney; D007680:Kidney Neoplasms / Q000473:pathology*; D008113:Liver Neoplasms; D008545:Melanoma; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics*; D000072260:RNA Splicing Factors; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D009396:Wilms Tumor / Q000473:pathology*
D051700:Activating Transcription Factor 3; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D000072260:RNA Splicing Factors; D012334:RNA, Neoplasm; C419554:WTAP protein, human