Impad1 and Syt11 Work in an Epistatic Pathway That Regulates EMT-mediated Vesicular Trafficking to Drive Lung Cancer Invasion and Metastasis

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2022 Sep 28

PMID 36170810

Authors

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

Affiliations

Soon will be listed here.

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.

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