التفاصيل البيبلوغرافية
| العنوان: |
Ki-67 regulates global gene expression and promotes sequential stages of carcinogenesis. |
| 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 |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 3/9/2021, Vol. 118 Issue 10, p1-12, 12p |
| مصطلحات موضوعية: |
KI-67 antigen, HISTOCOMPATIBILITY class I antigens, GENE expression, COMMERCIAL products, CURCUMIN |
| مستخلص: |
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 immunesuppressive environment that prevents the early phase of tumor regression. Finally, genes involved in xenobiotic metabolism are downregulated, 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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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