Senescence-associated reprogramming promotes cancer stemness

Senescence-associated reprogramming promotes cancer stemness Nature 553, 7686 (2018). doi:10.1038/nature25167 Authors: Maja Milanovic, Dorothy N. Y. Fan, Dimitri Belenki, J. Henry M. Däbritz, Zhen Zhao, Yong Yu, Jan R. Dörr, Lora Dimitrova, Dido Lenze, Ines A. Monteiro Barbosa, Marco A. Mendoza-Parra, Tamara Kanashova, Marlen Metzner, Katharina Pardon, Maurice Reimann, Andreas Trumpp, Bernd Dörken, Johannes Zuber, Hinrich Gronemeyer, Michael Hummel, Gunnar Dittmar, Soyoung Lee & Clemens A. Schmitt Cellular senescence is a stress-responsive cell-cycle arrest program that terminates the further expansion of (pre-)malignant cells. Key signalling components of the senescence machinery, such as p16INK4a, p21CIP1 and p53, as well as trimethylation of lysine 9 at histone H3 (H3K9me3), also operate as critical regulators of stem-cell functions (which are collectively termed ‘stemness’). In cancer cells, a gain of stemness may have profound implications for tumour aggressiveness and clinical outcome. Here we investigated whether chemotherapy-induced senescence could change stem-cell-related properties of malignant cells. Gene expression and functional analyses comparing senescent and non-senescent B-cell lymphomas from Eμ-Myc transgenic mice revealed substantial upregulation of an adult tissue stem-cell signature, activated Wnt signalling, and distinct ...
Source: Nature - Category: Research Authors: Tags: Letter Source Type: research