Stromal Expression of the Core Clock Gene Period 2 Is Essential for Tumor Initiation and Metastatic Colonization
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 tu...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-10-01
|
| Series: | Frontiers in Cell and Developmental Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2020.587697/full |
| _version_ | 1818776148553760768 |
|---|---|
| author | Lee Shaashua Shimrit Mayer Chen Lior Hagar Lavon Alexander Novoselsky Ruth Scherz-Shouval |
| author_facet | Lee Shaashua Shimrit Mayer Chen Lior Hagar Lavon Alexander Novoselsky Ruth Scherz-Shouval |
| author_sort | Lee Shaashua |
| collection | DOAJ |
| description | 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 gene Per2 in the TME is crucial for tumor initiation and metastatic colonization, whereas another core gene, Per1, is dispensable. We further show that loss of Per2 in 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 gene Per2 in the TME, with potential implications for therapeutic dosing strategies and treatment regimens. |
| first_indexed | 2024-12-18T11:08:20Z |
| format | Article |
| id | doaj.art-02e1d20eb2b240c0af25cf9b8f847cca |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-18T11:08:20Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-02e1d20eb2b240c0af25cf9b8f847cca2022-12-21T21:10:02ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-10-01810.3389/fcell.2020.587697587697Stromal Expression of the Core Clock Gene Period 2 Is Essential for Tumor Initiation and Metastatic ColonizationLee ShaashuaShimrit MayerChen LiorHagar LavonAlexander NovoselskyRuth Scherz-ShouvalThe 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 gene Per2 in the TME is crucial for tumor initiation and metastatic colonization, whereas another core gene, Per1, is dispensable. We further show that loss of Per2 in 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 gene Per2 in the TME, with potential implications for therapeutic dosing strategies and treatment regimens.https://www.frontiersin.org/article/10.3389/fcell.2020.587697/fullcircadian clockPer2tumor microenvironmentcolon cancerchronobiologymetastasis |
| spellingShingle | Lee Shaashua Shimrit Mayer Chen Lior Hagar Lavon Alexander Novoselsky Ruth Scherz-Shouval Stromal Expression of the Core Clock Gene Period 2 Is Essential for Tumor Initiation and Metastatic Colonization Frontiers in Cell and Developmental Biology circadian clock Per2 tumor microenvironment colon cancer chronobiology metastasis |
| title | Stromal Expression of the Core Clock Gene Period 2 Is Essential for Tumor Initiation and Metastatic Colonization |
| title_full | Stromal Expression of the Core Clock Gene Period 2 Is Essential for Tumor Initiation and Metastatic Colonization |
| title_fullStr | Stromal Expression of the Core Clock Gene Period 2 Is Essential for Tumor Initiation and Metastatic Colonization |
| title_full_unstemmed | Stromal Expression of the Core Clock Gene Period 2 Is Essential for Tumor Initiation and Metastatic Colonization |
| title_short | Stromal Expression of the Core Clock Gene Period 2 Is Essential for Tumor Initiation and Metastatic Colonization |
| title_sort | stromal expression of the core clock gene period 2 is essential for tumor initiation and metastatic colonization |
| topic | circadian clock Per2 tumor microenvironment colon cancer chronobiology metastasis |
| url | https://www.frontiersin.org/article/10.3389/fcell.2020.587697/full |
| work_keys_str_mv | AT leeshaashua stromalexpressionofthecoreclockgeneperiod2isessentialfortumorinitiationandmetastaticcolonization AT shimritmayer stromalexpressionofthecoreclockgeneperiod2isessentialfortumorinitiationandmetastaticcolonization AT chenlior stromalexpressionofthecoreclockgeneperiod2isessentialfortumorinitiationandmetastaticcolonization AT hagarlavon stromalexpressionofthecoreclockgeneperiod2isessentialfortumorinitiationandmetastaticcolonization AT alexandernovoselsky stromalexpressionofthecoreclockgeneperiod2isessentialfortumorinitiationandmetastaticcolonization AT ruthscherzshouval stromalexpressionofthecoreclockgeneperiod2isessentialfortumorinitiationandmetastaticcolonization |