Reference - Detail
| RRC ID | 78654 |
|---|---|
| Author | Masuda T, Fukuda A, Yamakawa G, Omatsu M, Namikawa M, Sono M, Fukunaga Y, Nagao M, Araki O, Yoshikawa T, Ogawa S, Masuo K, Goto N, Hiramatsu Y, Muta Y, Tsuda M, Maruno T, Nakanishi Y, Masui T, Hatano E, Matsuzaki T, Noda M, Seno H. |
| Title | Pancreatic RECK inactivation promotes cancer formation, epithelial-mesenchymal transition, and metastasis. |
| Journal | J Clin Invest |
| Abstract |
RECK is downregulated in various human cancers; however, how RECK inactivation affects carcinogenesis remains unclear. We addressed this issue in a pancreatic ductal adenocarcinoma (PDAC) mouse model and found that pancreatic Reck deletion dramatically augmented the spontaneous development of PDAC with a mesenchymal phenotype, which was accompanied by increased liver metastases and decreased survival. Lineage tracing revealed that pancreatic Reck deletion induced epithelial-mesenchymal transition (EMT) in PDAC cells, giving rise to inflammatory cancer-associated fibroblast-like cells in mice. Splenic transplantation of Reck-null PDAC cells resulted in numerous liver metastases with a mesenchymal phenotype, whereas reexpression of RECK markedly reduced metastases and changed the PDAC tumor phenotype into an epithelial one. Consistently, low RECK expression correlated with low E-cadherin expression, poor differentiation, metastasis, and poor prognosis in human PDAC. RECK reexpression in the PDAC cells was found to downregulate MMP2 and MMP3, with a concomitant increase in E-cadherin and decrease in EMT-promoting transcription factors. An MMP inhibitor recapitulated the effects of RECK on the expression of E-cadherin and EMT-promoting transcription factors and invasive activity. These results establish the authenticity of RECK as a pancreatic tumor suppressor, provide insights into its underlying mechanisms, and support the idea that RECK could be an important therapeutic effector against human PDAC. |
| Volume | 133(18) |
| Published | 2023-9-15 |
| DOI | 10.1172/JCI161847 |
| PII | 161847 |
| PMID | 37712427 |
| PMC | PMC10503799 |
| MeSH | Animals Cadherins / genetics Carcinoma, Pancreatic Ductal* / genetics Epithelial-Mesenchymal Transition / genetics GPI-Linked Proteins / genetics Humans Liver Neoplasms* / genetics Mice Pancreas Pancreatic Neoplasms* / genetics |
| IF | 11.864 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 8 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | PK45-P(RCB2141) PK45-H(RCB1973) PK-8(RCB2700) PK-59(RCB1901) KP-4(RCB1005) |