دورية أكاديمية

A local tumor microenvironment acquired super-enhancer induces an oncogenic driver in colorectal carcinoma

التفاصيل البيبلوغرافية
العنوان: A local tumor microenvironment acquired super-enhancer induces an oncogenic driver in colorectal carcinoma
المؤلفون: Zhou, Royce W., Xu, Jia, Martin, Tiphaine C., Zachem, Alexis L., He, John, Ozturk, Sait, Demircioglu, Deniz, Bansal, Ankita, Trotta, Andrew P., Giotti, Bruno, Gryder, Berkley, Shen, Yao, Wu, Xuewei, Carcamo, Saul, Bosch, Kaitlyn, Hopkins, Benjamin, Tsankov, Alexander, Steinhagen, Randolph, Jones, Drew R., Asara, John, Chipuk, Jerry E., Brody, Rachel, Itzkowitz, Steven, Chio, Iok In Christine, Hasson, Dan, Bernstein, Emily, Parsons, Ramon E.
المصدر: Nature Communications ; volume 13, issue 1 ; ISSN 2041-1723
بيانات النشر: Springer Science and Business Media LLC
سنة النشر: 2022
مصطلحات موضوعية: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary
الوصف: Tumors exhibit enhancer reprogramming compared to normal tissue. The etiology is largely attributed to cell-intrinsic genomic alterations. Here, using freshly resected primary CRC tumors and patient-matched adjacent normal colon, we find divergent epigenetic landscapes between CRC tumors and cell lines. Intriguingly, this phenomenon extends to highly recurrent aberrant super-enhancers gained in CRC over normal. We find one such super-enhancer activated in epithelial cancer cells due to surrounding inflammation in the tumor microenvironment. We restore this super-enhancer and its expressed gene, PDZK1IP1 , following treatment with cytokines or xenotransplantation into nude mice, thus demonstrating cell-extrinsic etiology. We demonstrate mechanistically that PDZK1IP1 enhances the reductive capacity CRC cancer cells via the pentose phosphate pathway. We show this activation enables efficient growth under oxidative conditions, challenging the previous notion that PDZK1IP1 acts as a tumor suppressor in CRC. Collectively, these observations highlight the significance of epigenomic profiling on primary specimens.
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1038/s41467-022-33377-8
الإتاحة: https://doi.org/10.1038/s41467-022-33377-8Test
https://www.nature.com/articles/s41467-022-33377-8.pdfTest
https://www.nature.com/articles/s41467-022-33377-8Test
حقوق: https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test
رقم الانضمام: edsbas.FF68C27F
قاعدة البيانات: BASE