Stromal Expression of the Core Clock GenePeriod 2Is Essential for Tumor Initiation and Metastatic Colonization
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Authors: Shaashua, Lee; Mayer, Shimrit; Lior, Chen; Lavon, Hagar; Novoselsky, Alexander; Scherz-Shouval, Ruth
Abstract
The circadian clock regulates diverse physiological processes by maintaining a 24-h gene expression pattern. Genetic and environmental cues that disrupt normal clock rhythms can lead to cancer, yet the extent to which this effect is controlled by the cancer cells versus non-malignant cells in the tumor microenvironment (TME) is not clear. Here we set out to address this question, by selective manipulation of circadian clock genes in the TME. In two different mouse models of cancer we find that expression of the core clock genePer2in the TME is crucial for tumor initiation and metastatic colonization, whereas another core gene,Per1, is dispensable. We further show that loss ofPer2in the TME leads to significant transcriptional changes in response to cancer cell introduction. These changes may contribute to a tumor-suppressive microenvironment. Thus, our work unravels an unexpected protumorigenic role for the core clock genePer2in the TME, with potential implications for therapeutic dosing strategies and treatment regimens.
Dwell-time based stability analysis and L-2 control of LPV systems with piecewise constant parameters and delay
SYSTEMS & CONTROL LETTERS
Authors: Zakwan, Muhammad; Ahmed, Saeed
Abstract
Dwell-time based stability conditions for a class of LPV systems with piecewise constant parameters under time-varying delay are derived using clock-dependent Lyapunov-Krasovskii functional. Sufficient synthesis conditions for clock-dependent gain-scheduled state-feedback controllers ensuring L-2-performance are also provided. Several numerical and practical examples, to illustrate the efficacy of the results, are given. (C) 2020 Elsevier B.V. All rights reserved.