Faculty, Staff and Student Publications
Publication Date
9-27-2022
Journal
Cell Reports
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.
Keywords
Cell Line, Tumor, Cell Movement, Epithelial-Mesenchymal Transition, Gene Expression Regulation, Neoplastic, Humans, Lung Neoplasms, MicroRNAs, Neoplasm Invasiveness, Neoplasm Metastasis, Synaptotagmins, Tumor Microenvironment, 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
DOI
10.1016/j.celrep.2022.111429
PMID
36170810
PMCID
PMC9665355
PubMedCentral® Posted Date
11-14-2022
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons