| First Author | Kim KH | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 5 | Pages | 101076 |
| PubMed ID | 32361596 | Mgi Jnum | J:306840 |
| Mgi Id | MGI:6717925 | Doi | 10.1016/j.isci.2020.101076 |
| Citation | Kim KH, et al. (2020) Dynamic Malignant Wave of Ribosome-Insulted Gut Niche via the Wnt-CTGF/CCN2 Circuit. iScience 23(5):101076 |
| abstractText | Stress-driven ribosome dysfunction triggers an eIF2alpha-mediated integrated stress response to maintain cellular homeostasis. Among four key eIF2alpha 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 beta-catenin in a negative feedback manner. Moreover, dwindling expression of the Wnt/beta-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. |
