IMPAD1 and KDELR2 drive invasion and metastasis by enhancing Golgi-mediated secretion
| Autor: | Samrat T. Kundu, Chad J. Creighton, Jared J. Fradette, Kenneth L. Scott, Caitlin L. Grzeskowiak, Rakhee Bajaj, Don L. Gibbons |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research Lung Neoplasms Vesicular Transport Proteins Fluorescent Antibody Technique Golgi Apparatus Matrix metalloproteinase Biology Article Metastasis 03 medical and health sciences symbols.namesake 0302 clinical medicine Cell Movement Cell Line Tumor Genetics medicine Humans Secretion Neoplasm Invasiveness Lung cancer Molecular Biology Cell Proliferation Regulation of gene expression Cell growth Cancer Golgi apparatus medicine.disease Matrix Metalloproteinases Phosphoric Monoester Hydrolases Gene Expression Regulation Neoplastic 030104 developmental biology 030220 oncology & carcinogenesis symbols Cancer research Disease Progression |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| Popis: | Summary Non-small cell lung cancer (NSCLC) is the deadliest form of cancer worldwide, due in part to its proclivity to metastasize. Identifying novel drivers of invasion and metastasis holds therapeutic potential for the disease. We conducted a gain-of-function invasion screen, which identified two separate hits, IMPAD1 and KDELR2, as robust, independent drivers of lung cancer invasion and metastasis. Given that IMPAD1 and KDELR2 are known to be localized to the ER-Golgi pathway, we studied their common mechanism of driving in vitro invasion and in vivo metastasis and demonstrated that they enhance Golgi-mediated function and secretion. Therapeutically inhibiting matrix metalloproteases (MMPs) suppressed both IMPAD1- and KDELR2-mediated invasion. The hits from this unbiased screen and the mechanistic validation highlight Golgi function as one of the key cellular features altered during invasion and metastasis. |
| Databáze: | OpenAIRE |
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