ArticleThe Journal of clinical investigation2017
Recurrent ubiquitin B silencing in gynecological cancers establishes dependence on ubiquitin C.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 32 citations in OpenAlex.
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- Tumor-intrinsic and -extrinsic (immune) gene signatures robustly predict overall survival and treatment response in high grade serous ovarian cancer patients.American journal of cancer research · 2021Article
- The Ubiquitin Gene Expression Pattern and Sensitivity toInternational journal of molecular sciences · 2020Article
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- Identification of Hub Genes in Pediatric Medulloblastoma by Multiple-Microarray Analysis.Journal of molecular neuroscience : MN · 2020Article
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- High-affinity free ubiquitin sensors for quantifying ubiquitin homeostasis and deubiquitination.Nature methods · 2019Article
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16 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Transcriptional repression of ubiquitin B (UBB) is a cancer-subtype-specific alteration that occurs in a substantial population of patients with cancers of the female reproductive tract. UBB is 1 of 2 genes encoding for ubiquitin as a polyprotein consisting of multiple copies of ubiquitin monomers. Silencing of UBB reduces cellular UBB levels and results in an exquisite dependence on ubiquitin C (UBC), the second polyubiquitin gene. UBB is repressed in approximately 30% of high-grade serous ovarian cancer (HGSOC) patients and is a recurrent lesion in uterine carcinosarcoma and endometrial carcinoma. We identified ovarian tumor cell lines that retain UBB in a repressed state, used these cell lines to establish orthotopic ovarian tumors, and found that inducible expression of a UBC-targeting shRNA led to tumor regression, and substantial long-term survival benefit. Thus, we describe a recurrent cancer-specific lesion at the level of ubiquitin production. Moreover, these observations reveal the prognostic value of UBB repression and establish UBC as a promising therapeutic target for ovarian cancer patients with recurrent UBB silencing.
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