Dynamic Malignant Wave of Ribosome-Insulted Gut Niche via the Wnt-CTGF/CCN2 Circuit
Summary: Stress-driven ribosome dysfunction triggers an eIF2α-mediated integrated stress response to maintain cellular homeostasis. Among four key eIF2α kinases, protein kinase R (PKR) expression positively associates with poor prognoses for colorectal cancer (CRC) patients. We identified PKR-linked...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-05-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004220302613 |
| _version_ | 1818119140128325632 |
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| author | Ki Hyung Kim Seung Joon Lee Juil Kim Yuseok Moon |
| author_facet | Ki Hyung Kim Seung Joon Lee Juil Kim Yuseok Moon |
| author_sort | Ki Hyung Kim |
| collection | DOAJ |
| description | Summary: Stress-driven ribosome dysfunction triggers an eIF2α-mediated integrated stress response to maintain cellular homeostasis. Among four key eIF2α kinases, protein kinase R (PKR) expression positively associates with poor prognoses for colorectal cancer (CRC) patients. We identified PKR-linked Wnt signaling networks that facilitate early inflammatory niche and epithelial-mesenchymal transitions of tumor tissues in response to ribosomal insults. However, the downstream Wnt signaling target fibrogenic connective tissue growth factor (CTGF/CCN2) regulates the nuclear translocation of β-catenin in a negative feedback manner. Moreover, dwindling expression of the Wnt/β-catenin pathway-regulator CTGF triggers noncanonical Wnt pathway-mediated exacerbation of intestinal cancer progression such as an increase in cancer stemness and acquisition of chemoresistance in the presence of ribosomal insults. The Wnt-CTGF-circuit-associated landscape of oncogenic signaling events was verified with clinical genomic profiling. This ribosome-associated wave of crosstalk between stress and oncogenes provides valuable insight into potential molecular interventions against intestinal malignancies. |
| first_indexed | 2024-12-11T05:05:28Z |
| format | Article |
| id | doaj.art-1899dd91fd0e49a68139d22bd5fc671f |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-11T05:05:28Z |
| publishDate | 2020-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-1899dd91fd0e49a68139d22bd5fc671f2022-12-22T01:20:02ZengElsevieriScience2589-00422020-05-01235Dynamic Malignant Wave of Ribosome-Insulted Gut Niche via the Wnt-CTGF/CCN2 CircuitKi Hyung Kim0Seung Joon Lee1Juil Kim2Yuseok Moon3Laboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University, Yangsan 50612, Korea; Department of Obstetrics and Gynecology, Pusan National University College of Medicine, Busan 49241, Korea; Biomedical Research Institute, Pusan National University Hospital, Busan, 49241, KoreaLaboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University, Yangsan 50612, KoreaLaboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University, Yangsan 50612, KoreaLaboratory of Mucosal Exposome and Biomodulation, Department of Biomedical Sciences, Pusan National University, Yangsan 50612, Korea; Biomedical Research Institute, Pusan National University Hospital, Busan, 49241, Korea; Corresponding authorSummary: Stress-driven ribosome dysfunction triggers an eIF2α-mediated integrated stress response to maintain cellular homeostasis. Among four key eIF2α kinases, protein kinase R (PKR) expression positively associates with poor prognoses for colorectal cancer (CRC) patients. We identified PKR-linked Wnt signaling networks that facilitate early inflammatory niche and epithelial-mesenchymal transitions of tumor tissues in response to ribosomal insults. However, the downstream Wnt signaling target fibrogenic connective tissue growth factor (CTGF/CCN2) regulates the nuclear translocation of β-catenin in a negative feedback manner. Moreover, dwindling expression of the Wnt/β-catenin pathway-regulator CTGF triggers noncanonical Wnt pathway-mediated exacerbation of intestinal cancer progression such as an increase in cancer stemness and acquisition of chemoresistance in the presence of ribosomal insults. The Wnt-CTGF-circuit-associated landscape of oncogenic signaling events was verified with clinical genomic profiling. This ribosome-associated wave of crosstalk between stress and oncogenes provides valuable insight into potential molecular interventions against intestinal malignancies.http://www.sciencedirect.com/science/article/pii/S2589004220302613Biological SciencesCell BiologyFunctional Aspects of Cell BiologyCancer |
| spellingShingle | Ki Hyung Kim Seung Joon Lee Juil Kim Yuseok Moon Dynamic Malignant Wave of Ribosome-Insulted Gut Niche via the Wnt-CTGF/CCN2 Circuit iScience Biological Sciences Cell Biology Functional Aspects of Cell Biology Cancer |
| title | Dynamic Malignant Wave of Ribosome-Insulted Gut Niche via the Wnt-CTGF/CCN2 Circuit |
| title_full | Dynamic Malignant Wave of Ribosome-Insulted Gut Niche via the Wnt-CTGF/CCN2 Circuit |
| title_fullStr | Dynamic Malignant Wave of Ribosome-Insulted Gut Niche via the Wnt-CTGF/CCN2 Circuit |
| title_full_unstemmed | Dynamic Malignant Wave of Ribosome-Insulted Gut Niche via the Wnt-CTGF/CCN2 Circuit |
| title_short | Dynamic Malignant Wave of Ribosome-Insulted Gut Niche via the Wnt-CTGF/CCN2 Circuit |
| title_sort | dynamic malignant wave of ribosome insulted gut niche via the wnt ctgf ccn2 circuit |
| topic | Biological Sciences Cell Biology Functional Aspects of Cell Biology Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004220302613 |
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