دورية أكاديمية
Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis
| العنوان: | Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis |
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| المؤلفون: | Mrouj, Karim, Andrés-Sánchez, Nuria, Dubra, Geronimo, Singh, Priyanka, Sobecki, Michal, Chahar, Dhanvantri, Al Ghoul, Emile, Aznar, Ana Bella, Prieto, Susana, Pirot, Nelly, Bernex, Florence, Bordignon, Benoit, Hassen-Khodja, Cedric, Villalba, Martin, Krasinska, Liliana, Fisher, Daniel |
| المساهمون: | Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Montpellier (UM), Regional Imaging Platform, Montpellier Ressources Imagerie (MRI), BioCampus, Montpellier, France, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire Montpellier (CHRU Montpellier) |
| المصدر: | ISSN: 0027-8424. |
| بيانات النشر: | HAL CCSD National Academy of Sciences |
| سنة النشر: | 2021 |
| المجموعة: | Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe) |
| مصطلحات موضوعية: | Ki-67, cancer, genetically modified mice, transcription, [SDV]Life Sciences [q-bio] |
| الوصف: | International audience ; Ki-67 is a nuclear protein that is expressed in all proliferating vertebrate cells. Here, we demonstrate that, although Ki-67 is not required for cell proliferation, its genetic ablation inhibits each step of tumor initiation, growth, and metastasis. Mice lacking Ki-67 are resistant to chemical or genetic induction of intestinal tumorigenesis. In established cancer cells, Ki-67 knockout causes global transcriptome remodeling that alters the epithelial–mesenchymal balance and suppresses stem cell characteristics. When grafted into mice, tumor growth is slowed, and metastasis is abrogated, despite normal cell proliferation rates. Yet, Ki-67 loss also down-regulates major histocompatibility complex class I antigen presentation and, in the 4T1 syngeneic model of mammary carcinoma, leads to an immune-suppressive environment that prevents the early phase of tumor regression. Finally, genes involved in xenobiotic metabolism are down-regulated, and cells are sensitized to various drug classes. Our results suggest that Ki-67 enables transcriptional programs required for cellular adaptation to the environment. This facilitates multiple steps of carcinogenesis and drug resistance, yet may render cancer cells more susceptible to antitumor immune responses. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | hal-03364397; https://hal.archives-ouvertes.fr/hal-03364397Test; https://hal.archives-ouvertes.fr/hal-03364397/documentTest; https://hal.archives-ouvertes.fr/hal-03364397/file/Ki67%20Karim%20Mrouj%20PNAS%20final%20version%20accepted%20300121.pdfTest |
| DOI: | 10.1073/pnas.2026507118 |
| الإتاحة: | https://doi.org/10.1073/pnas.2026507118Test https://hal.archives-ouvertes.fr/hal-03364397Test https://hal.archives-ouvertes.fr/hal-03364397/documentTest https://hal.archives-ouvertes.fr/hal-03364397/file/Ki67%20Karim%20Mrouj%20PNAS%20final%20version%20accepted%20300121.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.5D886C04 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1073/pnas.2026507118 |
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