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β-Arrestin2 mediates the initiation and progression of myeloid leukemia
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , |
| In: | Proceedings of the National Academy of Sciences, 109, 2012, 31, S. 12532-12537 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| author_facet |
Fereshteh, Mark Ito, Takahiro Kovacs, Jeffrey J. Zhao, Chen Kwon, Hyog Young Tornini, Valerie Konuma, Takaaki Chen, Minyong Lefkowitz, Robert J. Reya, Tannishtha Fereshteh, Mark Ito, Takahiro Kovacs, Jeffrey J. Zhao, Chen Kwon, Hyog Young Tornini, Valerie Konuma, Takaaki Chen, Minyong Lefkowitz, Robert J. Reya, Tannishtha |
|---|---|
| author |
Fereshteh, Mark Ito, Takahiro Kovacs, Jeffrey J. Zhao, Chen Kwon, Hyog Young Tornini, Valerie Konuma, Takaaki Chen, Minyong Lefkowitz, Robert J. Reya, Tannishtha |
| spellingShingle |
Fereshteh, Mark Ito, Takahiro Kovacs, Jeffrey J. Zhao, Chen Kwon, Hyog Young Tornini, Valerie Konuma, Takaaki Chen, Minyong Lefkowitz, Robert J. Reya, Tannishtha Proceedings of the National Academy of Sciences β-Arrestin2 mediates the initiation and progression of myeloid leukemia Multidisciplinary |
| author_sort |
fereshteh, mark |
| spelling |
Fereshteh, Mark Ito, Takahiro Kovacs, Jeffrey J. Zhao, Chen Kwon, Hyog Young Tornini, Valerie Konuma, Takaaki Chen, Minyong Lefkowitz, Robert J. Reya, Tannishtha 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.1209815109 <jats:p>β-Arrestins were initially discovered as negative regulators of G protein-coupled receptor signaling. Although β-arrestins have more recently been implicated as scaffold proteins that interact with various mitogenic and developmental signals, the genetic role of β-arrestins in driving oncogenesis is not known. Here we have investigated the role of β-arrestin in hematologic malignancies and have found that although both β-arrestin1 and -2 are expressed in the hematopoietic system, loss of β-arrestin2 preferentially leads to a severe impairment in the establishment and propagation of the chronic and blast crisis phases of chronic myelogenous leukemia (CML). These defects are linked to a reduced frequency, as well as defective self-renewal capacity of the cancer stem-cell population, in mouse models and in human CML patient samples. At a molecular level, the loss of β-arrestin2 leads to a significant inhibition of β-catenin stabilization, and ectopic activation of Wnt signaling reverses the defects observed in the β-arrestin2 mutant cells. These data cumulatively show that β-arrestin2 is essential for CML disease propagation and indicate that β-arrestins and the Wnt/β-catenin pathway lie in a signaling hierarchy in the context of CML cancer stem cell maintenance.</jats:p> β-Arrestin2 mediates the initiation and progression of myeloid leukemia Proceedings of the National Academy of Sciences |
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| title |
β-Arrestin2 mediates the initiation and progression of myeloid leukemia |
| title_unstemmed |
β-Arrestin2 mediates the initiation and progression of myeloid leukemia |
| title_full |
β-Arrestin2 mediates the initiation and progression of myeloid leukemia |
| title_fullStr |
β-Arrestin2 mediates the initiation and progression of myeloid leukemia |
| title_full_unstemmed |
β-Arrestin2 mediates the initiation and progression of myeloid leukemia |
| title_short |
β-Arrestin2 mediates the initiation and progression of myeloid leukemia |
| title_sort |
β-arrestin2 mediates the initiation and progression of myeloid leukemia |
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Multidisciplinary |
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http://dx.doi.org/10.1073/pnas.1209815109 |
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2012 |
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12532-12537 |
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<jats:p>β-Arrestins were initially discovered as negative regulators of G protein-coupled receptor signaling. Although β-arrestins have more recently been implicated as scaffold proteins that interact with various mitogenic and developmental signals, the genetic role of β-arrestins in driving oncogenesis is not known. Here we have investigated the role of β-arrestin in hematologic malignancies and have found that although both β-arrestin1 and -2 are expressed in the hematopoietic system, loss of β-arrestin2 preferentially leads to a severe impairment in the establishment and propagation of the chronic and blast crisis phases of chronic myelogenous leukemia (CML). These defects are linked to a reduced frequency, as well as defective self-renewal capacity of the cancer stem-cell population, in mouse models and in human CML patient samples. At a molecular level, the loss of β-arrestin2 leads to a significant inhibition of β-catenin stabilization, and ectopic activation of Wnt signaling reverses the defects observed in the β-arrestin2 mutant cells. These data cumulatively show that β-arrestin2 is essential for CML disease propagation and indicate that β-arrestins and the Wnt/β-catenin pathway lie in a signaling hierarchy in the context of CML cancer stem cell maintenance.</jats:p> |
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| author | Fereshteh, Mark, Ito, Takahiro, Kovacs, Jeffrey J., Zhao, Chen, Kwon, Hyog Young, Tornini, Valerie, Konuma, Takaaki, Chen, Minyong, Lefkowitz, Robert J., Reya, Tannishtha |
| author_facet | Fereshteh, Mark, Ito, Takahiro, Kovacs, Jeffrey J., Zhao, Chen, Kwon, Hyog Young, Tornini, Valerie, Konuma, Takaaki, Chen, Minyong, Lefkowitz, Robert J., Reya, Tannishtha, Fereshteh, Mark, Ito, Takahiro, Kovacs, Jeffrey J., Zhao, Chen, Kwon, Hyog Young, Tornini, Valerie, Konuma, Takaaki, Chen, Minyong, Lefkowitz, Robert J., Reya, Tannishtha |
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| description | <jats:p>β-Arrestins were initially discovered as negative regulators of G protein-coupled receptor signaling. Although β-arrestins have more recently been implicated as scaffold proteins that interact with various mitogenic and developmental signals, the genetic role of β-arrestins in driving oncogenesis is not known. Here we have investigated the role of β-arrestin in hematologic malignancies and have found that although both β-arrestin1 and -2 are expressed in the hematopoietic system, loss of β-arrestin2 preferentially leads to a severe impairment in the establishment and propagation of the chronic and blast crisis phases of chronic myelogenous leukemia (CML). These defects are linked to a reduced frequency, as well as defective self-renewal capacity of the cancer stem-cell population, in mouse models and in human CML patient samples. At a molecular level, the loss of β-arrestin2 leads to a significant inhibition of β-catenin stabilization, and ectopic activation of Wnt signaling reverses the defects observed in the β-arrestin2 mutant cells. These data cumulatively show that β-arrestin2 is essential for CML disease propagation and indicate that β-arrestins and the Wnt/β-catenin pathway lie in a signaling hierarchy in the context of CML cancer stem cell maintenance.</jats:p> |
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| spelling | Fereshteh, Mark Ito, Takahiro Kovacs, Jeffrey J. Zhao, Chen Kwon, Hyog Young Tornini, Valerie Konuma, Takaaki Chen, Minyong Lefkowitz, Robert J. Reya, Tannishtha 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.1209815109 <jats:p>β-Arrestins were initially discovered as negative regulators of G protein-coupled receptor signaling. Although β-arrestins have more recently been implicated as scaffold proteins that interact with various mitogenic and developmental signals, the genetic role of β-arrestins in driving oncogenesis is not known. Here we have investigated the role of β-arrestin in hematologic malignancies and have found that although both β-arrestin1 and -2 are expressed in the hematopoietic system, loss of β-arrestin2 preferentially leads to a severe impairment in the establishment and propagation of the chronic and blast crisis phases of chronic myelogenous leukemia (CML). These defects are linked to a reduced frequency, as well as defective self-renewal capacity of the cancer stem-cell population, in mouse models and in human CML patient samples. At a molecular level, the loss of β-arrestin2 leads to a significant inhibition of β-catenin stabilization, and ectopic activation of Wnt signaling reverses the defects observed in the β-arrestin2 mutant cells. These data cumulatively show that β-arrestin2 is essential for CML disease propagation and indicate that β-arrestins and the Wnt/β-catenin pathway lie in a signaling hierarchy in the context of CML cancer stem cell maintenance.</jats:p> β-Arrestin2 mediates the initiation and progression of myeloid leukemia Proceedings of the National Academy of Sciences |
| spellingShingle | Fereshteh, Mark, Ito, Takahiro, Kovacs, Jeffrey J., Zhao, Chen, Kwon, Hyog Young, Tornini, Valerie, Konuma, Takaaki, Chen, Minyong, Lefkowitz, Robert J., Reya, Tannishtha, Proceedings of the National Academy of Sciences, β-Arrestin2 mediates the initiation and progression of myeloid leukemia, Multidisciplinary |
| title | β-Arrestin2 mediates the initiation and progression of myeloid leukemia |
| title_full | β-Arrestin2 mediates the initiation and progression of myeloid leukemia |
| title_fullStr | β-Arrestin2 mediates the initiation and progression of myeloid leukemia |
| title_full_unstemmed | β-Arrestin2 mediates the initiation and progression of myeloid leukemia |
| title_short | β-Arrestin2 mediates the initiation and progression of myeloid leukemia |
| title_sort | β-arrestin2 mediates the initiation and progression of myeloid leukemia |
| title_unstemmed | β-Arrestin2 mediates the initiation and progression of myeloid leukemia |
| topic | Multidisciplinary |
| url | http://dx.doi.org/10.1073/pnas.1209815109 |