title: Exo70 isoform switching upon epithelial-mesenchymal transition mediates cancer cell invasion.
abstract: Epithelial-mesenchymal transition (EMT) is an important developmental process hijacked by cancer cells for their dissemination. Here, we show that Exo70, a component of the exocyst complex, undergoes isoform switching mediated by ESRP1, a pre-mRNA splicing factor that regulates EMT. Expression of the epithelial isoform of Exo70 affects the levels of key EMT transcriptional regulators such as Snail and ZEB2 and is sufficient to drive the transition to epithelial phenotypes. Differential Exo70 isoform expression in human tumors correlates with cancer progression, and increased expression of the epithelial isoform of Exo70 inhibits tumor metastasis in mice. At the molecular level, the mesenchymal-but not the epithelial-isoform of Exo70 interacts with the Arp2/3 complex and stimulates actin polymerization for tumor invasion. Our findings provide a mechanism by which the exocyst function and actin dynamics are modulated for EMT and tumor invasion.
authors: Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Hezhe
authors: H
authors: Lu
authors: Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Jianglan
authors: J
authors: Liu
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Shujing
authors: S
authors: Liu
authors: Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Jingwen
authors: J
authors: Zeng
authors: Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou 311121, China.
authors: Deqiang
authors: D
authors: Ding
authors: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Russ P
authors: RP
authors: Carstens
authors: Institute of Aging Research, Hangzhou Normal University School of Medicine, Hangzhou 311121, China.
authors: Yusheng
authors: Y
authors: Cong
authors: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Xiaowei
authors: X
authors: Xu
authors: Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: guowei@sas.upenn.edu.
authors: Wei
authors: W
authors: Guo
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000378:metabolism; D017398:Alternative Splicing / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000556:secondary*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051376:Actin-Related Protein 2-3 Complex; C539364:ESRP1 protein, human; C547754:EXOC7 protein, human; D016601:RNA-Binding Proteins; D033921:Vesicular Transport Proteins