| First Author | Tang Q | Year | 2021 |
| Journal | EMBO Rep | Volume | 22 |
| Issue | 2 | Pages | e48351 |
| PubMed ID | 33403789 | Mgi Jnum | J:306297 |
| Mgi Id | MGI:6712139 | Doi | 10.15252/embr.201948351 |
| Citation | Tang Q, et al. (2021) Rab11-FIP1 mediates epithelial-mesenchymal transition and invasion in esophageal cancer. EMBO Rep 22(2):e48351 |
| abstractText | Esophageal squamous cell carcinoma (ESCC) is the most common subtype of esophageal cancer worldwide. The most commonly mutated gene in ESCC is TP53. Using a combinatorial genetic and carcinogenic approach, we generate a novel mouse model of ESCC expressing either mutant or null p53 and show that mutant p53 exhibits enhanced tumorigenic properties and displays a distinct genomic profile. Through RNA-seq analysis, we identify several endocytic recycling genes, including Rab Coupling Protein (Rab11-FIP1), which are significantly downregulated in mutant p53 tumor cells. In 3-dimensional (3D) organoid models, genetic knockdown of Rab11-FIP1 results in increased organoid size. Loss of Rab11-FIP1 increases tumor cell invasion in part through mutant p53 but also in an independent manner. Furthermore, loss of Rab11-FIP1 in human ESCC cell lines decreases E-cadherin expression and increases mesenchymal lineage-specific markers, suggesting induction of epithelial-mesenchymal transition (EMT). Rab11-FIP1 regulates EMT through direct inhibition of Zeb1, a key EMT transcriptional factor. Our novel findings reveal that Rab11-FIP1 regulates organoid formation, tumor cell invasion, and EMT. |
