Rab11-FIP1 mediates epithelial-mesenchymal transition and invasion in esophageal cancer

Qiaosi Tang, A. Lento, K. Suzuki, G. Efe, Tatiana Karakasheva, A. Long, Veronique Giroux, Mirazul Islam, E. P. Wileyto, Andrés J.P. Klein-Szanto, H. Nakagawa, Adam J. Bass, A. K. Rustgi

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

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.
Original languageAmerican English
Article numbere48351
Pages (from-to)e48351
JournalEMBO Reports
Volume22
Issue number2
DOIs
StatePublished - Feb 3 2021
Externally publishedYes

Keywords

  • *Carcinoma, Squamous Cell/genetics Cell Line, Tumor Cell Movement/genetics Cell Proliferation Epithelial-Mesenchymal Transition/genetics *Esophageal Neoplasms/genetics *Esophageal Squamous Cell Carcinoma/genetics Gene Expression Regulation, Neoplastic Humans Neoplasm Invasiveness Epithelial-Mesenchymal transition Rab coupling protein (Rab11-FIP1) esophageal cancer invasion
  • Cell Movement/genetics
  • Carcinoma, Squamous Cell/genetics
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition/genetics
  • Esophageal Neoplasms/genetics
  • Neoplasm Invasiveness
  • Humans
  • Gene Expression Regulation, Neoplastic
  • Cell Line, Tumor
  • Esophageal Squamous Cell Carcinoma/genetics

Fingerprint

Dive into the research topics of 'Rab11-FIP1 mediates epithelial-mesenchymal transition and invasion in esophageal cancer'. Together they form a unique fingerprint.

Cite this