An Interaction with Ewing’s Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate Cancer
Summary: More than 50% of prostate tumors have a chromosomal rearrangement resulting in aberrant expression of an oncogenic ETS family transcription factor. However, mechanisms that differentiate the function of oncogenic ETS factors expressed in prostate tumors from non-oncogenic ETS factors expres...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2016-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716313705 |
| _version_ | 1828793778286100480 |
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| author | Vivekananda Kedage Nagarathinam Selvaraj Taylor R. Nicholas Justin A. Budka Joshua P. Plotnik Travis J. Jerde Peter C. Hollenhorst |
| author_facet | Vivekananda Kedage Nagarathinam Selvaraj Taylor R. Nicholas Justin A. Budka Joshua P. Plotnik Travis J. Jerde Peter C. Hollenhorst |
| author_sort | Vivekananda Kedage |
| collection | DOAJ |
| description | Summary: More than 50% of prostate tumors have a chromosomal rearrangement resulting in aberrant expression of an oncogenic ETS family transcription factor. However, mechanisms that differentiate the function of oncogenic ETS factors expressed in prostate tumors from non-oncogenic ETS factors expressed in normal prostate are unknown. Here, we find that four oncogenic ETS (ERG, ETV1, ETV4, and ETV5), and no other ETS, interact with the Ewing’s sarcoma breakpoint protein, EWS. This EWS interaction was necessary and sufficient for oncogenic ETS functions including gene activation, cell migration, clonogenic survival, and transformation. Significantly, the EWS interacting region of ERG has no homology with that of ETV1, ETV4, and ETV5. Therefore, this finding may explain how divergent ETS factors have a common oncogenic function. Strikingly, EWS is fused to various ETS factors by the chromosome translocations that cause Ewing’s sarcoma. Therefore, these findings link oncogenic ETS function in both prostate cancer and Ewing’s sarcoma. : A subset of ETS transcription factors is oncogenic in prostate. Kedage et al. show that oncogenic ETS, but not other ETS, interact with EWS, and this interaction is necessary for oncogenic functions. Because EWS is fused to ETS factors in Ewing’s sarcoma, this finding links the mechanisms of these diseases. Keywords: prostate cancer, ETS, EWS, Ewing’s sarcoma, ERG |
| first_indexed | 2024-12-12T03:33:37Z |
| format | Article |
| id | doaj.art-875f7987522647da9e3288a80e15b123 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-12T03:33:37Z |
| publishDate | 2016-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-875f7987522647da9e3288a80e15b1232022-12-22T00:39:52ZengElsevierCell Reports2211-12472016-10-0117512891301An Interaction with Ewing’s Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate CancerVivekananda Kedage0Nagarathinam Selvaraj1Taylor R. Nicholas2Justin A. Budka3Joshua P. Plotnik4Travis J. Jerde5Peter C. Hollenhorst6Department of Molecular and Cellular Biochemistry, Indiana University, Bloomington, IN 47405, USAMedical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USADepartment of Biology, Indiana University, Bloomington, IN 47405, USAMedical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USADepartment of Biology, Indiana University, Bloomington, IN 47405, USADepartment of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USAMedical Sciences, Indiana University School of Medicine, Bloomington, IN 47405, USA; Corresponding authorSummary: More than 50% of prostate tumors have a chromosomal rearrangement resulting in aberrant expression of an oncogenic ETS family transcription factor. However, mechanisms that differentiate the function of oncogenic ETS factors expressed in prostate tumors from non-oncogenic ETS factors expressed in normal prostate are unknown. Here, we find that four oncogenic ETS (ERG, ETV1, ETV4, and ETV5), and no other ETS, interact with the Ewing’s sarcoma breakpoint protein, EWS. This EWS interaction was necessary and sufficient for oncogenic ETS functions including gene activation, cell migration, clonogenic survival, and transformation. Significantly, the EWS interacting region of ERG has no homology with that of ETV1, ETV4, and ETV5. Therefore, this finding may explain how divergent ETS factors have a common oncogenic function. Strikingly, EWS is fused to various ETS factors by the chromosome translocations that cause Ewing’s sarcoma. Therefore, these findings link oncogenic ETS function in both prostate cancer and Ewing’s sarcoma. : A subset of ETS transcription factors is oncogenic in prostate. Kedage et al. show that oncogenic ETS, but not other ETS, interact with EWS, and this interaction is necessary for oncogenic functions. Because EWS is fused to ETS factors in Ewing’s sarcoma, this finding links the mechanisms of these diseases. Keywords: prostate cancer, ETS, EWS, Ewing’s sarcoma, ERGhttp://www.sciencedirect.com/science/article/pii/S2211124716313705 |
| spellingShingle | Vivekananda Kedage Nagarathinam Selvaraj Taylor R. Nicholas Justin A. Budka Joshua P. Plotnik Travis J. Jerde Peter C. Hollenhorst An Interaction with Ewing’s Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate Cancer Cell Reports |
| title | An Interaction with Ewing’s Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate Cancer |
| title_full | An Interaction with Ewing’s Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate Cancer |
| title_fullStr | An Interaction with Ewing’s Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate Cancer |
| title_full_unstemmed | An Interaction with Ewing’s Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate Cancer |
| title_short | An Interaction with Ewing’s Sarcoma Breakpoint Protein EWS Defines a Specific Oncogenic Mechanism of ETS Factors Rearranged in Prostate Cancer |
| title_sort | interaction with ewing s sarcoma breakpoint protein ews defines a specific oncogenic mechanism of ets factors rearranged in prostate cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716313705 |
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