IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53
Cancer stem cells (CSCs) are considered tumor-initiating cells and the main drivers of disease progression. Targeting these rare cancer cells, however, remains challenging with respect to therapeutic benefit. Here, we report the up-regulation of IL-13RA2 expression in colorectal cancer (CRC) tissues...
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KeAi Communications Co., Ltd.
2024-01-01
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| Series: | Genes and Diseases |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304223000521 |
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| author | Baoyu He Jing Liang Qianqian Qin Yuqin Zhang Shuo Shi Jinghe Cao Zhixin Zhang Qingli Bie Rou Zhao Li Wei Baogui Zhang Bin Zhang |
| author_facet | Baoyu He Jing Liang Qianqian Qin Yuqin Zhang Shuo Shi Jinghe Cao Zhixin Zhang Qingli Bie Rou Zhao Li Wei Baogui Zhang Bin Zhang |
| author_sort | Baoyu He |
| collection | DOAJ |
| description | Cancer stem cells (CSCs) are considered tumor-initiating cells and the main drivers of disease progression. Targeting these rare cancer cells, however, remains challenging with respect to therapeutic benefit. Here, we report the up-regulation of IL-13RA2 expression in colorectal cancer (CRC) tissues and spheroid cells. The expression of IL-13RA2 was positively correlated with canonical stemness markers in CRC. We further demonstrated that the level of IL-13 was up-regulated in the serum of CRC patients. Biologically, recombinant IL-13 (rIL-13) stimulation promoted the sphere formation, proliferation, and migration of CRC cells in vitro and enhanced tumorigenesis in vivo. This phenotype could be reversed by knocking down IL-13RA2. Mechanistically, IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs, which was crucial for the biological functions of IL-13. We further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein, enhancing the interaction of UBE3C and p53, thereby inducing the K48-linked ubiquitination of p53. In conclusion, the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination, adding an important layer to the connection between IL-13 and p53, which can be translated into novel targeted therapies. |
| first_indexed | 2024-03-12T15:20:07Z |
| format | Article |
| id | doaj.art-ae33ca951d3644d289e7f68adb413cfb |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-12T15:20:07Z |
| publishDate | 2024-01-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-ae33ca951d3644d289e7f68adb413cfb2023-08-11T05:34:50ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422024-01-01111495508IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53Baoyu He0Jing Liang1Qianqian Qin2Yuqin Zhang3Shuo Shi4Jinghe Cao5Zhixin Zhang6Qingli Bie7Rou Zhao8Li Wei9Baogui Zhang10Bin Zhang11Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272000, China; Postdoctoral Mobile Station of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, ChinaDepartment of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272000, ChinaDepartment of Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272000, ChinaDepartment of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272000, ChinaDepartment of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272000, ChinaDepartment of Reproductive Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272000, ChinaDepartment of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272000, ChinaDepartment of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272000, China; Postdoctoral Mobile Station of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, ChinaDepartment of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272000, ChinaDepartment of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272000, ChinaDepartment of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272000, China; Corresponding author. Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, 89 Guhuai Road, Jining, Shandong 272000, China.Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong 272000, China; Postdoctoral Mobile Station of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China; Institute of Forensic Medicine and Laboratory Medicine, Jining Medical University, Jining, Shandong 272067, China; Corresponding author. Department of Laboratory Medicine, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong 272000, China.Cancer stem cells (CSCs) are considered tumor-initiating cells and the main drivers of disease progression. Targeting these rare cancer cells, however, remains challenging with respect to therapeutic benefit. Here, we report the up-regulation of IL-13RA2 expression in colorectal cancer (CRC) tissues and spheroid cells. The expression of IL-13RA2 was positively correlated with canonical stemness markers in CRC. We further demonstrated that the level of IL-13 was up-regulated in the serum of CRC patients. Biologically, recombinant IL-13 (rIL-13) stimulation promoted the sphere formation, proliferation, and migration of CRC cells in vitro and enhanced tumorigenesis in vivo. This phenotype could be reversed by knocking down IL-13RA2. Mechanistically, IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs, which was crucial for the biological functions of IL-13. We further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein, enhancing the interaction of UBE3C and p53, thereby inducing the K48-linked ubiquitination of p53. In conclusion, the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination, adding an important layer to the connection between IL-13 and p53, which can be translated into novel targeted therapies.http://www.sciencedirect.com/science/article/pii/S2352304223000521AutophagyColorectal cancer stem cellsIL-13/IL-13RA2 signalingp53Ubiquitinated degradation |
| spellingShingle | Baoyu He Jing Liang Qianqian Qin Yuqin Zhang Shuo Shi Jinghe Cao Zhixin Zhang Qingli Bie Rou Zhao Li Wei Baogui Zhang Bin Zhang IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53 Genes and Diseases Autophagy Colorectal cancer stem cells IL-13/IL-13RA2 signaling p53 Ubiquitinated degradation |
| title | IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53 |
| title_full | IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53 |
| title_fullStr | IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53 |
| title_full_unstemmed | IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53 |
| title_short | IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53 |
| title_sort | il 13 il 13ra2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53 |
| topic | Autophagy Colorectal cancer stem cells IL-13/IL-13RA2 signaling p53 Ubiquitinated degradation |
| url | http://www.sciencedirect.com/science/article/pii/S2352304223000521 |
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