EB1 acts as an oncogene via activating beta-catenin/TCF pathway to promote cellular growth and inhibit apoptosis.
Previously we showed that end-binding protein 1 (EB1) may promote cellular growth by activating beta-catenin/T-cell factor (TCF) pathway. To further investigate the role of EB1 in regulating cellular growth, we established an EB1-inducible expression system in which the protein level of EB1 was significantly upregulated upon doxycycline induction. We found that EB1 promoted cellular growth and resulted in a significant increase in colony formation. In addition, EB1 could induce tumor formation in nude mice, activate beta-catenin-dependent gene expression and upregulate the transcriptional activity of c-myc. We also showed that EB1 in this manner inhibited apoptosis of 293-T-REx cells upon cisplatin and upregulated expression of Bcl-2, whereas DeltaN TCF4, an inhibitor of beta-catenin/TCF pathway, could completely or partially abolish the effects of EB1 on the promotion of cell growth and the inhibition of apoptosis activity. Moreover, knockdown of c-myc by RNAi could abrogate upregulation of EB1-dependent induction of Bcl-2 expression. Overall, EB1 acts as a potential oncogene via activating beta-catenin/TCF pathway to promote cellular growth and inhibit apoptosis.
Liu
Mei
M
Laboratory of Cell and Molecular Biology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
Yang
Shangbin
S
Laboratory of Cell and Molecular Biology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.|Department of Pathology, Ohio State University, Columbus, Ohio.
Wang
Yihua
Y
Laboratory of Cell and Molecular Biology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.|Signal Transduction Laboratory, London Research Institute, Lincoln's Inn Fields Laboratories, Cancer Research UK (CR-UK), London, UK.
Zhu
Hongxia
H
Laboratory of Cell and Molecular Biology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
Yan
Shuang
S
Laboratory of Cell and Molecular Biology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
Zhang
Wei
W
Laboratory of Cell and Molecular Biology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
Quan
Lanping
L
Laboratory of Cell and Molecular Biology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
Bai
Jinfeng
J
Laboratory of Cell and Molecular Biology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
Xu
Ningzhi
N
Laboratory of Cell and Molecular Biology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D000970:Antineoplastic Agents; C495270:CTNNB1 protein, human; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D051820:TCF Transcription Factors; D051176:beta Catenin; D002945:Cisplatin