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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.
AuthorsHezhe Lu, Jianglan Liu, Shujing Liu, Jingwen Zeng, Deqiang Ding, Russ P Carstens, Yusheng Cong, Xiaowei Xu, Wei Guo
JournalDevelopmental cell (Dev Cell) Vol. 27 Issue 5 Pg. 560-73 (Dec 09 2013) ISSN: 1878-1551 [Electronic] United States
PMID24331928 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2013 Elsevier Inc. All rights reserved.
Chemical References
  • Actin-Related Protein 2-3 Complex
  • ESRP1 protein, human
  • EXOC7 protein, human
  • RNA-Binding Proteins
  • Vesicular Transport Proteins
Topics
  • Actin-Related Protein 2-3 Complex (metabolism)
  • Alternative Splicing (physiology)
  • Amino Acid Sequence
  • Animals
  • Breast Neoplasms (genetics, secondary)
  • Disease Progression
  • Epithelial-Mesenchymal Transition (physiology)
  • Female
  • Heterografts
  • Humans
  • MCF-7 Cells
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Neoplasm Invasiveness
  • Neoplasm Transplantation
  • RNA-Binding Proteins (genetics, metabolism)
  • Vesicular Transport Proteins (genetics, metabolism)

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