Impad1 and Syt11 work in an epistatic pathway that regulates EMT-mediated vesicular trafficking to drive lung cancer invasion and metastasis

Rakhee Bajaj, B. Leticia Rodriguez, William K. Russell, Amanda N. Warner, Lixia Diao, Jing Wang, Maria G. Raso, Wei Lu, Khaja Khan, Luisa S. Solis, Harsh Batra, Ximing Tang, Jared F. Fradette, Samrat T. Kundu, Don L. Gibbons

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Lung cancer is a highly aggressive and metastatic disease responsible for approximately 25% of all cancer-related deaths in the United States. Using high-throughput in vitro and in vivo screens, we have previously established Impad1 as a driver of lung cancer invasion and metastasis. Here we elucidate that Impad1 is a direct target of the epithelial microRNAs (miRNAs) miR-200 and miR∼96 and is de-repressed during epithelial-to-mesenchymal transition (EMT); thus, we establish a mode of regulation of the protein. Impad1 modulates Golgi apparatus morphology and vesicular trafficking through its interaction with a trafficking protein, Syt11. These changes in Golgi apparatus dynamics alter the extracellular matrix and the tumor microenvironment (TME) to promote invasion and metastasis. Inhibiting Impad1 or Syt11 disrupts the cancer cell secretome, regulates the TME, and reverses the invasive or metastatic phenotype. This work identifies Impad1 as a regulator of EMT and secretome-mediated changes during lung cancer progression.

Original languageEnglish (US)
Article number111429
JournalCell Reports
Volume40
Issue number13
DOIs
StatePublished - Sep 27 2022

Keywords

  • CP: Cancer
  • Golgi exocytosis
  • Golgi morphology
  • Impad1
  • Syt11
  • epithelial-to-mesenchymal transition
  • extracellular matrix
  • invasion
  • lung cancer
  • metastasis
  • secretome
  • tumor immune microenvironment
  • tumor microenvironment
  • vesicular trafficking

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

MD Anderson CCSG core facilities

  • Research Animal Support Facility
  • Tissue Biospecimen and Pathology Resource
  • Bioinformatics Shared Resource
  • Flow Cytometry and Cellular Imaging Facility

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