Abstract
Misregulation of the Wnt signaling pathway has been linked to many human cancers including colon carcinoma and melanoma. The primary mediator of the oncogenic effects of the Wnt signaling pathway is β-catenin. Accumulation of nuclear β-catenin and transcription activation of lymphoid enhancer factor 1 (LEF1)/T-cell factor (TCF) target genes underlie the oncogenic activity. However, the mechanism of β-catenin-mediated transcriptional activation remains poorly understood. In this study, we identified Mastermind-like 1 (Maml1), which is thought to be a specific coactivator for the Notch pathway, as a coactivator for β-catenin. We found that Maml1 participates in the Wnt signaling by modulating the β-catenin/TCF activity. We show in vivo that Maml1 is recruited by β-catenin on the cyclin D1 and c-Myc promoters. Importantly, we show that Maml1 functions in the Wnt/β-catenin pathway independently of Notch signaling. Finally, we show that the knockdown of Mastermind-like family proteins in colonic carcinoma cells results in cell death by affecting β-catenin-induced expression of cyclin D1 and c-Myc. This is the first demonstration of a role for the Mastermind-like family in another signaling pathway and that the knockdown of Mastermind-like family function leads to tumor cell death.
| Original language | English |
|---|---|
| Pages (from-to) | 8690-8698 |
| Number of pages | 9 |
| Journal | Cancer Research |
| Volume | 67 |
| Issue number | 18 |
| DOIs | |
| State | Published - Sep 15 2007 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Mastermind-like 1 is a specific coactivator of β-catenin transcription activation and is essential for colon carcinoma cell survival. / Alves-Guerra, Marie Clotilde; Ronchini, Chiara; Capobianco, Anthony J.
In: Cancer Research, Vol. 67, No. 18, 15.09.2007, p. 8690-8698.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mastermind-like 1 is a specific coactivator of β-catenin transcription activation and is essential for colon carcinoma cell survival
AU - Alves-Guerra, Marie Clotilde
AU - Ronchini, Chiara
AU - Capobianco, Anthony J
PY - 2007/9/15
Y1 - 2007/9/15
N2 - Misregulation of the Wnt signaling pathway has been linked to many human cancers including colon carcinoma and melanoma. The primary mediator of the oncogenic effects of the Wnt signaling pathway is β-catenin. Accumulation of nuclear β-catenin and transcription activation of lymphoid enhancer factor 1 (LEF1)/T-cell factor (TCF) target genes underlie the oncogenic activity. However, the mechanism of β-catenin-mediated transcriptional activation remains poorly understood. In this study, we identified Mastermind-like 1 (Maml1), which is thought to be a specific coactivator for the Notch pathway, as a coactivator for β-catenin. We found that Maml1 participates in the Wnt signaling by modulating the β-catenin/TCF activity. We show in vivo that Maml1 is recruited by β-catenin on the cyclin D1 and c-Myc promoters. Importantly, we show that Maml1 functions in the Wnt/β-catenin pathway independently of Notch signaling. Finally, we show that the knockdown of Mastermind-like family proteins in colonic carcinoma cells results in cell death by affecting β-catenin-induced expression of cyclin D1 and c-Myc. This is the first demonstration of a role for the Mastermind-like family in another signaling pathway and that the knockdown of Mastermind-like family function leads to tumor cell death.
AB - Misregulation of the Wnt signaling pathway has been linked to many human cancers including colon carcinoma and melanoma. The primary mediator of the oncogenic effects of the Wnt signaling pathway is β-catenin. Accumulation of nuclear β-catenin and transcription activation of lymphoid enhancer factor 1 (LEF1)/T-cell factor (TCF) target genes underlie the oncogenic activity. However, the mechanism of β-catenin-mediated transcriptional activation remains poorly understood. In this study, we identified Mastermind-like 1 (Maml1), which is thought to be a specific coactivator for the Notch pathway, as a coactivator for β-catenin. We found that Maml1 participates in the Wnt signaling by modulating the β-catenin/TCF activity. We show in vivo that Maml1 is recruited by β-catenin on the cyclin D1 and c-Myc promoters. Importantly, we show that Maml1 functions in the Wnt/β-catenin pathway independently of Notch signaling. Finally, we show that the knockdown of Mastermind-like family proteins in colonic carcinoma cells results in cell death by affecting β-catenin-induced expression of cyclin D1 and c-Myc. This is the first demonstration of a role for the Mastermind-like family in another signaling pathway and that the knockdown of Mastermind-like family function leads to tumor cell death.
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UR - http://www.scopus.com/inward/citedby.url?scp=34548708035&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-1720
DO - 10.1158/0008-5472.CAN-07-1720
M3 - Article
C2 - 17875709
AN - SCOPUS:34548708035
VL - 67
SP - 8690
EP - 8698
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 18
ER -