@article{988678da1eef47e18801979d9f238857,
title = "Impad1 and Syt11 work in an epistatic pathway that regulates EMT-mediated vesicular trafficking to drive lung cancer invasion and metastasis",
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 = "CP: Cancer, epithelial-to-mesenchymal transition, extracellular matrix, Golgi exocytosis, Golgi morphology, Impad1, invasion, lung cancer, metastasis, secretome, Syt11, tumor immune microenvironment, tumor microenvironment, vesicular trafficking",
author = "Rakhee Bajaj and Rodriguez, {B. Leticia} and Russell, {William K.} and Warner, {Amanda N.} and Lixia Diao and Jing Wang and Raso, {Maria G.} and Wei Lu and Khaja Khan and Solis, {Luisa S.} and Harsh Batra and Ximing Tang and Fradette, {Jared F.} and Kundu, {Samrat T.} and Gibbons, {Don L.}",
note = "Funding Information: This work was supported by NIH R37CA214609 , NIH 2P50CA070907-21A , CPRIT-MIRA RP160652-P3 , the MD Anderson Physician-Scientist Program, and Rexanna{\textquoteright}s Foundation for Fighting Lung Cancer (to D.L.G.). R.B. was supported by a CPRIT Research Training Grant ( RP170067 ). The work was also supported by generous philanthropic contributions to The University of Texas MD Anderson Lung Cancer Moon Shots Program. We thank the UTMDACC Department of Veterinary Medicine facility. The Flow Cytometry Lab South Campus Core facility at MD Anderson Cancer Center is supported by Cancer Center Support Grant NCI P30 CA16672 . The mass spectrometry facility at UTMB is supported in part by Cancer Prevention Research Institute of Texas (CPRIT) grant RP190682 . Funding Information: This work was supported by NIH R37CA214609, NIH 2P50CA070907-21A, CPRIT-MIRA RP160652-P3, the MD Anderson Physician-Scientist Program, and Rexanna's Foundation for Fighting Lung Cancer (to D.L.G.). R.B. was supported by a CPRIT Research Training Grant (RP170067). The work was also supported by generous philanthropic contributions to The University of Texas MD Anderson Lung Cancer Moon Shots Program. We thank the UTMDACC Department of Veterinary Medicine facility. The Flow Cytometry Lab South Campus Core facility at MD Anderson Cancer Center is supported by Cancer Center Support Grant NCI P30 CA16672. The mass spectrometry facility at UTMB is supported in part by Cancer Prevention Research Institute of Texas (CPRIT) grant RP190682. Study conceptualization, design, and execution of project, R.B. and D.L.G.; data acquisition and statistical analysis, R.B. B.L.R. and A.N.W.; mass spectrometry, W.K.R.; bioinformatics analysis for mRNA and miRNA correlations in human cell lines and tumors, L.D. and J.W.; IHC on human lung cancer specimens, W.L. K.K. and L.S.S.; digital image analysis, H.B.; mouse model generation and maintenance, J.F.F. and S.T.K.; overall supervision of IHC staining, M.G.R.; analysis, interpretation, and representation of data, R.B.; manuscript writing, critical revision, and preparation of figures and tables, R.B. J.F.F. A.N.W. and D.L.G.; overall supervision and execution, D.L.G. D.L.G. declares advisory board work for AstraZeneca, Eli Lilly, Menarini Richerche, 4D Pharma, and Sanofi. D.L.G. has received research grant funding from AstraZeneca, Janssen, Astellas, Ribon Therapeutics, NGM Biotherapeutics, and Takeda. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = sep,
day = "27",
doi = "10.1016/j.celrep.2022.111429",
language = "English (US)",
volume = "40",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "13",
}