The CIC-ERF co-deletion underlies fusion-independent activation of ETS family member, ETV1, to drive prostate cancer progression
Human prostate cancer can result from chromosomal rearrangements that lead to aberrant ETS gene expression. The mechanisms that lead to fusion-independent ETS factor upregulation and prostate oncogenesis remain relatively unknown. Here, we show that two neighboring transcription factors, Capicua (CI...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2022-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/77072 |
| _version_ | 1828193918815043584 |
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| author | Nehal Gupta Hanbing Song Wei Wu Rovingaile K Ponce Yone K Lin Ji Won Kim Eric J Small Felix Y Feng Franklin W Huang Ross A Okimoto |
| author_facet | Nehal Gupta Hanbing Song Wei Wu Rovingaile K Ponce Yone K Lin Ji Won Kim Eric J Small Felix Y Feng Franklin W Huang Ross A Okimoto |
| author_sort | Nehal Gupta |
| collection | DOAJ |
| description | Human prostate cancer can result from chromosomal rearrangements that lead to aberrant ETS gene expression. The mechanisms that lead to fusion-independent ETS factor upregulation and prostate oncogenesis remain relatively unknown. Here, we show that two neighboring transcription factors, Capicua (CIC) and ETS2 repressor factor (ERF), which are co-deleted in human prostate tumors can drive prostate oncogenesis. Concurrent CIC and ERF loss commonly occur through focal genomic deletions at chromosome 19q13.2. Mechanistically, CIC and ERF co-bind the proximal regulatory element and mutually repress the ETS transcription factor, ETV1. Targeting ETV1 in CIC and ERF-deficient prostate cancer limits tumor growth. Thus, we have uncovered a fusion-independent mode of ETS transcriptional activation defined by concurrent loss of CIC and ERF. |
| first_indexed | 2024-04-12T09:15:38Z |
| format | Article |
| id | doaj.art-0eb13355c7624b8981b2504410da190b |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:15:38Z |
| publishDate | 2022-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0eb13355c7624b8981b2504410da190b2022-12-22T03:38:50ZengeLife Sciences Publications LtdeLife2050-084X2022-11-011110.7554/eLife.77072The CIC-ERF co-deletion underlies fusion-independent activation of ETS family member, ETV1, to drive prostate cancer progressionNehal Gupta0https://orcid.org/0000-0002-8931-5759Hanbing Song1Wei Wu2Rovingaile K Ponce3Yone K Lin4Ji Won Kim5Eric J Small6Felix Y Feng7Franklin W Huang8https://orcid.org/0000-0001-5447-0436Ross A Okimoto9https://orcid.org/0000-0002-4467-8476Department of Medicine, University of California, San Francisco, United StatesDepartment of Medicine, University of California, San Francisco, United StatesDepartment of Medicine, University of California, San Francisco, United StatesDepartment of Medicine, University of California, San Francisco, United StatesDepartment of Medicine, University of California, San Francisco, United StatesDepartment of Medicine, University of California, San Francisco, United StatesDepartment of Medicine, University of California, San Francisco, United States; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, United StatesDepartment of Medicine, University of California, San Francisco, United States; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, United States; Department of Radiation Oncology, University of California, San Francisco, United StatesDepartment of Medicine, University of California, San Francisco, United States; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, United StatesDepartment of Medicine, University of California, San Francisco, United States; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, United StatesHuman prostate cancer can result from chromosomal rearrangements that lead to aberrant ETS gene expression. The mechanisms that lead to fusion-independent ETS factor upregulation and prostate oncogenesis remain relatively unknown. Here, we show that two neighboring transcription factors, Capicua (CIC) and ETS2 repressor factor (ERF), which are co-deleted in human prostate tumors can drive prostate oncogenesis. Concurrent CIC and ERF loss commonly occur through focal genomic deletions at chromosome 19q13.2. Mechanistically, CIC and ERF co-bind the proximal regulatory element and mutually repress the ETS transcription factor, ETV1. Targeting ETV1 in CIC and ERF-deficient prostate cancer limits tumor growth. Thus, we have uncovered a fusion-independent mode of ETS transcriptional activation defined by concurrent loss of CIC and ERF.https://elifesciences.org/articles/77072prostate cancerCapicuaERFETS transcription factors |
| spellingShingle | Nehal Gupta Hanbing Song Wei Wu Rovingaile K Ponce Yone K Lin Ji Won Kim Eric J Small Felix Y Feng Franklin W Huang Ross A Okimoto The CIC-ERF co-deletion underlies fusion-independent activation of ETS family member, ETV1, to drive prostate cancer progression eLife prostate cancer Capicua ERF ETS transcription factors |
| title | The CIC-ERF co-deletion underlies fusion-independent activation of ETS family member, ETV1, to drive prostate cancer progression |
| title_full | The CIC-ERF co-deletion underlies fusion-independent activation of ETS family member, ETV1, to drive prostate cancer progression |
| title_fullStr | The CIC-ERF co-deletion underlies fusion-independent activation of ETS family member, ETV1, to drive prostate cancer progression |
| title_full_unstemmed | The CIC-ERF co-deletion underlies fusion-independent activation of ETS family member, ETV1, to drive prostate cancer progression |
| title_short | The CIC-ERF co-deletion underlies fusion-independent activation of ETS family member, ETV1, to drive prostate cancer progression |
| title_sort | cic erf co deletion underlies fusion independent activation of ets family member etv1 to drive prostate cancer progression |
| topic | prostate cancer Capicua ERF ETS transcription factors |
| url | https://elifesciences.org/articles/77072 |
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