Electronic Resource
In vivo epigenetic reprogramming of primary human colon cancer cells enhances metastases
| العنوان: | In vivo epigenetic reprogramming of primary human colon cancer cells enhances metastases |
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| المؤلفون: | Singovski, Grigori, Bernal, Carolina, Kuciak, Monika, Siegl-Cachedenier, Irene, Conod, Arwen, Ruiz i Altaba, Ariel |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | How metastases develop is not well understood and no genetic mutations have been reported as specific metastatic drivers. Here we have addressed the idea that epigenetic reprogramming by GLI-regulated pluripotent stemness factors promotes metastases. Using primary human colon cancer cells engrafted in mice, we find that transient expression of OCT4, SOX2, KLF4 +/− cMYC establishes an enhanced pro-metastatic state in the primary tumor that is stable through sequential engraftments and is transmitted through clonogenic cancer stem cells. Metastatic reprogramming alters NANOG methylation and stably boosts NANOG and NANOGP8 expression. Metastases and reprogrammed EMT-like phenotypes require endogenous NANOG, but enhanced NANOG is not sufficient to induce these phenotypes. Finally, reprogrammed tumors enhance GLI2, and we show that GLI2high and AXIN2low, which are markers of the metastatic transition of colon cancers, are prognostic of poor disease outcome in patients. We propose that metastases arise through epigenetic reprogramming of cancer stem cells within primary tumors. |
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| الاتاحة: | Open access content. Open access content |
| ملاحظة: | English |
| Other Numbers: | CHRRO oai:doc.rero.ch:331528 1283966779 |
| المصدر المساهم: | RERO-LIBR NETWORK OF WESTERN SWITZERLAND From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1283966779 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |