Kaydedildi:
| Yazar: | |
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| Materyal Türü: | Recurso digital |
| Dil: | |
| Baskı/Yayın Bilgisi: |
Zenodo
2025
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| Online Erişim: | https://doi.org/10.5281/zenodo.14993765 |
| Etiketler: |
Etiketle
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İçindekiler:
- <p>We recently described Xist induction (and in some cases its silencing), as a recurrent transcriptional event associated with p53-deficient backgrounds, and demonstrated Xist activation is directly controlled by loss of tumor suppressor (p53 or Rb) function. Xist expression is high soon after the onset of transformation; in some cancer types, like breast cancer, its expression remains high while in others its expression levels subside but remain detectable at clinical presentation of solid tumors. Xist activation is functionally relevant, as it influences clonal selection early in disease evidenced by its control of subtype selection in human breast cancer and human lung cancer. We used proteomic and transcriptomic techniques to identify the existence of a putative Xist RNP complex in cancer whose composition varies based on context and expression but whose major function appears to be modulation of interleukin enhancer factors ILF2/3 and likely possesses epigenetic silencing and activation functions reminiscent of its function in development but with a wider range of transcriptional targets. </p> <p><strong> </strong></p> <p>Resistance to treatment and disease relapse is a major problem in humans with cancer (solid tumor disease). We demonstrate here that Xist activation is a transcriptional feature of disease resistance, providing evidence that its activation is a quantitatively significant event in triple negative breast cancer cells displaying resistance to treatment. Thus, in human cancer, Xist is activated and a function is associated with this activation, at least twice: immediately after transformation, shaping clonal selection of the founder clone during stages that shape subtype selection, then reactivating later in disease, after treatment has begun, where its expression is enriched at high levels in TNBC patients with treatment-resistant disease, indicating its function both in development of the tumor but as a disease-modifying agent late in disease. </p> <p> </p>