biostudies-otherUnknownMs. Qiaosi TangAmerican Cancer Society (ACS)HHS | NIH | National Cancer Institute (NCI)EMBO Reportshttps://www.ebi.ac.uk/biostudies/studies/S-SCDT-EMBOR-2019-48351V1PEsophageal 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.biostudies-otherP01-CA098101Research Professorship (AKR)P30-CA01369645Ms. Qiaosi TangE. Paul WileytoAdam BassDr. Tatiana KarakashevaDr. Ashley, A. LentoDr. Kensuke SuzukiGizem EfeVéronique GirouxDr. Hiroshi NakagawaDr. Anil, K. RustgiApple LongAndres, J. Klein-SzantoMr. Mirazul IslamfalseRab11-FIP1 mediates Epithelial-Mesenchymal Transition and invasion in esophageal cancerEsophageal 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.2021-02-15T00:00:00Z2021-02-15T21:00:22Z2021-02-15T21:00:22ZS-SCDT-EMBOR-2019-48351V1P10.15252/embr.201948351