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Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma
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| Zeitschriftentitel: | Cancer Research |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , |
| In: | Cancer Research, 76, 2016, 21, S. 6382-6395 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Association for Cancer Research (AACR)
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| Schlagwörter: |
| author_facet |
Li, Huaibiao Frappart, Lucien Moll, Jürgen Winkler, Anne Kroll, Torsten Hamann, Jana Kufferath, Iris Groth, Marco Taudien, Stefan Schütte, Moritz Yaspo, Marie-Laure Heuer, Heike Lange, Bodo M.H. Platzer, Matthias Zatloukal, Kurt Herrlich, Peter Ploubidou, Aspasia Li, Huaibiao Frappart, Lucien Moll, Jürgen Winkler, Anne Kroll, Torsten Hamann, Jana Kufferath, Iris Groth, Marco Taudien, Stefan Schütte, Moritz Yaspo, Marie-Laure Heuer, Heike Lange, Bodo M.H. Platzer, Matthias Zatloukal, Kurt Herrlich, Peter Ploubidou, Aspasia |
|---|---|
| author |
Li, Huaibiao Frappart, Lucien Moll, Jürgen Winkler, Anne Kroll, Torsten Hamann, Jana Kufferath, Iris Groth, Marco Taudien, Stefan Schütte, Moritz Yaspo, Marie-Laure Heuer, Heike Lange, Bodo M.H. Platzer, Matthias Zatloukal, Kurt Herrlich, Peter Ploubidou, Aspasia |
| spellingShingle |
Li, Huaibiao Frappart, Lucien Moll, Jürgen Winkler, Anne Kroll, Torsten Hamann, Jana Kufferath, Iris Groth, Marco Taudien, Stefan Schütte, Moritz Yaspo, Marie-Laure Heuer, Heike Lange, Bodo M.H. Platzer, Matthias Zatloukal, Kurt Herrlich, Peter Ploubidou, Aspasia Cancer Research Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma Cancer Research Oncology |
| author_sort |
li, huaibiao |
| spelling |
Li, Huaibiao Frappart, Lucien Moll, Jürgen Winkler, Anne Kroll, Torsten Hamann, Jana Kufferath, Iris Groth, Marco Taudien, Stefan Schütte, Moritz Yaspo, Marie-Laure Heuer, Heike Lange, Bodo M.H. Platzer, Matthias Zatloukal, Kurt Herrlich, Peter Ploubidou, Aspasia 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-16-0179 <jats:title>Abstract</jats:title> <jats:p>Hypofertility is a risk factor for the development of testicular germ cell tumors (TGCT), but the initiating event linking these pathologies is unknown. We hypothesized that excessive planar division of undifferentiated germ cells promotes their self-renewal and TGCT development. However, our results obtained from mouse models and seminoma patients demonstrated the opposite. Defective planar divisions of undifferentiated germ cells caused their premature exit from the seminiferous tubule niche, resulting in germ cell depletion, hypofertility, intratubular germ cell neoplasias, and seminoma development. Oriented divisions of germ cells, which determine their fate, were regulated by spindle-associated RHAMM—a function we found to be abolished in 96% of human seminomas. Mechanistically, RHAMM expression is regulated by the testis-specific polyadenylation protein CFIm25, which is downregulated in the human seminomas. These results suggested that spindle misorientation is oncogenic, not by promoting self-renewing germ cell divisions within the niche, but by prematurely displacing proliferating cells from their normal epithelial milieu. Furthermore, they suggested RHAMM loss-of-function and spindle misorientation as an initiating event underlying both hypofertility and TGCT initiation. These findings identify spindle-associated RHAMM as an intrinsic regulator of male germ cell fate and as a gatekeeper preventing initiation of TGCTs. Cancer Res; 76(21); 6382–95. ©2016 AACR.</jats:p> Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma Cancer Research |
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| title |
Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma |
| title_unstemmed |
Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma |
| title_full |
Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma |
| title_fullStr |
Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma |
| title_full_unstemmed |
Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma |
| title_short |
Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma |
| title_sort |
impaired planar germ cell division in the testis, caused by dissociation of rhamm from the spindle, results in hypofertility and seminoma |
| topic |
Cancer Research Oncology |
| url |
http://dx.doi.org/10.1158/0008-5472.can-16-0179 |
| publishDate |
2016 |
| physical |
6382-6395 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Hypofertility is a risk factor for the development of testicular germ cell tumors (TGCT), but the initiating event linking these pathologies is unknown. We hypothesized that excessive planar division of undifferentiated germ cells promotes their self-renewal and TGCT development. However, our results obtained from mouse models and seminoma patients demonstrated the opposite. Defective planar divisions of undifferentiated germ cells caused their premature exit from the seminiferous tubule niche, resulting in germ cell depletion, hypofertility, intratubular germ cell neoplasias, and seminoma development. Oriented divisions of germ cells, which determine their fate, were regulated by spindle-associated RHAMM—a function we found to be abolished in 96% of human seminomas. Mechanistically, RHAMM expression is regulated by the testis-specific polyadenylation protein CFIm25, which is downregulated in the human seminomas. These results suggested that spindle misorientation is oncogenic, not by promoting self-renewing germ cell divisions within the niche, but by prematurely displacing proliferating cells from their normal epithelial milieu. Furthermore, they suggested RHAMM loss-of-function and spindle misorientation as an initiating event underlying both hypofertility and TGCT initiation. These findings identify spindle-associated RHAMM as an intrinsic regulator of male germ cell fate and as a gatekeeper preventing initiation of TGCTs. Cancer Res; 76(21); 6382–95. ©2016 AACR.</jats:p> |
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| author | Li, Huaibiao, Frappart, Lucien, Moll, Jürgen, Winkler, Anne, Kroll, Torsten, Hamann, Jana, Kufferath, Iris, Groth, Marco, Taudien, Stefan, Schütte, Moritz, Yaspo, Marie-Laure, Heuer, Heike, Lange, Bodo M.H., Platzer, Matthias, Zatloukal, Kurt, Herrlich, Peter, Ploubidou, Aspasia |
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| description | <jats:title>Abstract</jats:title> <jats:p>Hypofertility is a risk factor for the development of testicular germ cell tumors (TGCT), but the initiating event linking these pathologies is unknown. We hypothesized that excessive planar division of undifferentiated germ cells promotes their self-renewal and TGCT development. However, our results obtained from mouse models and seminoma patients demonstrated the opposite. Defective planar divisions of undifferentiated germ cells caused their premature exit from the seminiferous tubule niche, resulting in germ cell depletion, hypofertility, intratubular germ cell neoplasias, and seminoma development. Oriented divisions of germ cells, which determine their fate, were regulated by spindle-associated RHAMM—a function we found to be abolished in 96% of human seminomas. Mechanistically, RHAMM expression is regulated by the testis-specific polyadenylation protein CFIm25, which is downregulated in the human seminomas. These results suggested that spindle misorientation is oncogenic, not by promoting self-renewing germ cell divisions within the niche, but by prematurely displacing proliferating cells from their normal epithelial milieu. Furthermore, they suggested RHAMM loss-of-function and spindle misorientation as an initiating event underlying both hypofertility and TGCT initiation. These findings identify spindle-associated RHAMM as an intrinsic regulator of male germ cell fate and as a gatekeeper preventing initiation of TGCTs. Cancer Res; 76(21); 6382–95. ©2016 AACR.</jats:p> |
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| spelling | Li, Huaibiao Frappart, Lucien Moll, Jürgen Winkler, Anne Kroll, Torsten Hamann, Jana Kufferath, Iris Groth, Marco Taudien, Stefan Schütte, Moritz Yaspo, Marie-Laure Heuer, Heike Lange, Bodo M.H. Platzer, Matthias Zatloukal, Kurt Herrlich, Peter Ploubidou, Aspasia 0008-5472 1538-7445 American Association for Cancer Research (AACR) Cancer Research Oncology http://dx.doi.org/10.1158/0008-5472.can-16-0179 <jats:title>Abstract</jats:title> <jats:p>Hypofertility is a risk factor for the development of testicular germ cell tumors (TGCT), but the initiating event linking these pathologies is unknown. We hypothesized that excessive planar division of undifferentiated germ cells promotes their self-renewal and TGCT development. However, our results obtained from mouse models and seminoma patients demonstrated the opposite. Defective planar divisions of undifferentiated germ cells caused their premature exit from the seminiferous tubule niche, resulting in germ cell depletion, hypofertility, intratubular germ cell neoplasias, and seminoma development. Oriented divisions of germ cells, which determine their fate, were regulated by spindle-associated RHAMM—a function we found to be abolished in 96% of human seminomas. Mechanistically, RHAMM expression is regulated by the testis-specific polyadenylation protein CFIm25, which is downregulated in the human seminomas. These results suggested that spindle misorientation is oncogenic, not by promoting self-renewing germ cell divisions within the niche, but by prematurely displacing proliferating cells from their normal epithelial milieu. Furthermore, they suggested RHAMM loss-of-function and spindle misorientation as an initiating event underlying both hypofertility and TGCT initiation. These findings identify spindle-associated RHAMM as an intrinsic regulator of male germ cell fate and as a gatekeeper preventing initiation of TGCTs. Cancer Res; 76(21); 6382–95. ©2016 AACR.</jats:p> Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma Cancer Research |
| spellingShingle | Li, Huaibiao, Frappart, Lucien, Moll, Jürgen, Winkler, Anne, Kroll, Torsten, Hamann, Jana, Kufferath, Iris, Groth, Marco, Taudien, Stefan, Schütte, Moritz, Yaspo, Marie-Laure, Heuer, Heike, Lange, Bodo M.H., Platzer, Matthias, Zatloukal, Kurt, Herrlich, Peter, Ploubidou, Aspasia, Cancer Research, Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma, Cancer Research, Oncology |
| title | Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma |
| title_full | Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma |
| title_fullStr | Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma |
| title_full_unstemmed | Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma |
| title_short | Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma |
| title_sort | impaired planar germ cell division in the testis, caused by dissociation of rhamm from the spindle, results in hypofertility and seminoma |
| title_unstemmed | Impaired Planar Germ Cell Division in the Testis, Caused by Dissociation of RHAMM from the Spindle, Results in Hypofertility and Seminoma |
| topic | Cancer Research, Oncology |
| url | http://dx.doi.org/10.1158/0008-5472.can-16-0179 |