دورية أكاديمية
Chemerin enhances mesenchymal features of glioblastoma by establishing autocrine and paracrine networks in a CMKLR1-dependent manner
| العنوان: | Chemerin enhances mesenchymal features of glioblastoma by establishing autocrine and paracrine networks in a CMKLR1-dependent manner |
|---|---|
| المؤلفون: | Wu, Jianqi, Shen, Shuai, Liu, Tianqi, Ren, Xiufang, Zhu, Chen, Liang, Qingyu, Cui, Xiao, Chen, Ling, Cheng, Peng, Cheng, Wen, Wu, Anhua |
| المصدر: | Oncogene ; volume 41, issue 21, page 3024-3036 ; ISSN 0950-9232 1476-5594 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Genetics, Molecular Biology |
| الوصف: | Glioblastoma multiforme (GBM) with mesenchymal features exhibits enhanced chemotherapeutic resistance and results in reduced overall survival. Recent studies have suggested that there is a positive correlation between the GBM mesenchymal status and immune cell infiltration. However, the mechanisms by which GBM acquires its mesenchymal features in a tumor immune microenvironment-dependent manner remains unknown. Here, we uncovered a chemerin-mediated autocrine and paracrine network by which the mesenchymal phenotype of GBM cells is strengthened. We identified chemerin as a prognostic secretory protein mediating the mesenchymal phenotype-promoting network between tumor-associated macrophages (TAMs) and tumor cells in GBM. Mechanistically, chemerin promoted the mesenchymal features of GBM by suppressing the ubiquitin-proteasomal degradation of CMKLR1, a chemerin receptor predominantly expressed on TAMs and partially expressed on GBM cells, thereby enhancing NF-κB pathway activation. Moreover, chemerin was found to be involved in the recruitment of TAMs in the GBM tumor microenvironment. We revealed that chemerin also enhances the mesenchymal phenotype-promoting ability of TAMs and promotes their M2 polarization via a CMKLR1/NF-κB axis, which further exacerbates the mesenchymal features of GBM. Blocking the chemerin/CMKLR1 axis with 2-(α-naphthoyl) ethyltrimethylammonium iodide disrupted the mesenchymal network and suppressed tumor growth in GBM. These results suggest the therapeutic potential of targeting the chemerin/CMKLR1 axis to block the mesenchymal network in GBM. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41388-022-02295-w |
| الإتاحة: | https://doi.org/10.1038/s41388-022-02295-wTest https://www.nature.com/articles/s41388-022-02295-w.pdfTest https://www.nature.com/articles/s41388-022-02295-wTest |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.4A6E5204 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41388-022-02295-w |
|---|