G9a controls pluripotent-like identity and tumor-initiating function in human colorectal cancer
| العنوان: | G9a controls pluripotent-like identity and tumor-initiating function in human colorectal cancer |
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| المؤلفون: | François M. Desrochers, Yannick D. Benoit, Simon Y. Reilley, Christopher J. Bergin, Aïcha Zouggar, Angelique N. Masibag, Gautam Agrawal, Joshua R. Haebe |
| المصدر: | Oncogene |
| بيانات النشر: | Nature Publishing Group UK, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cancer Research, Biology, Brief Communication, Epigenesis, Genetic, 03 medical and health sciences, Prognostic markers, 0302 clinical medicine, Cancer stem cell, Histocompatibility Antigens, Histone post-translational modifications, Genetics, medicine, Humans, Epigenetics, Cell Self Renewal, Molecular Biology, Cancer stem cells, Wnt signaling pathway, Cancer, Histone-Lysine N-Methyltransferase, medicine.disease, Cellular Reprogramming, HCT116 Cells, Embryonic stem cell, Progression-Free Survival, 3. Good health, Gene Expression Regulation, Neoplastic, 030104 developmental biology, 030220 oncology & carcinogenesis, Histone methyltransferase, Cancer research, Carcinogens, Neoplastic Stem Cells, Female, Stem cell, Neoplasm Recurrence, Local, Colorectal Neoplasms, Transcriptome, Reprogramming |
| الوصف: | Colorectal tumors are hierarchically organized and governed by populations of self-renewing cancer stem cells, representing one of the deadliest types of cancers worldwide. Emergence of cancer stemness phenotype depends on epigenetic reprogramming, associated with profound transcriptional changes. As described for pluripotent reprogramming, epigenetic modifiers play a key role in cancer stem cells by establishing embryonic stem-like transcriptional programs, thus impacting the balance between self-renewal and differentiation. We identified overexpression of histone methyltransferase G9a as a risk factor for colorectal cancer, associated with shorter relapse-free survival. Moreover, using human transformed pluripotent cells as a surrogate model for cancer stem cells, we observed that G9a activity is essential for the maintenance of embryonic-like transcriptional signature promoting self-renewal, tumorigenicity, and undifferentiated state. Such a role was also applicable to colorectal cancer, where inhibitors of G9a histone methyltransferase function induced intestinal differentiation while restricting tumor-initiating activity in patient-derived colorectal tumor samples. Finally, by integrating transcriptome profiling with G9a/H3K9me2 loci co-occupancy, we identified the canonical Wnt pathway, epithelial-to-mesenchyme transition, and extracellular matrix organization as potential targets of such a chromatin regulation mechanism in colorectal cancer stem cells. Overall, our findings provide novel insights on the role of G9a as a driver of cancer stem cell phenotype, promoting self-renewal, tumorigenicity, and undifferentiated state. |
| اللغة: | English |
| تدمد: | 1476-5594 0950-9232 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9576d9c7fb9204c4f0c80db49ca72fe9Test http://europepmc.org/articles/PMC7878189Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9576d9c7fb9204c4f0c80db49ca72fe9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765594 09509232 |
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