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IMPAD1 and KDELR2 drive invasion and metastasis by enhancing Golgi-mediated secretion.

ABSTRACT: 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.

SUBMITTER: Bajaj R

PROVIDER: S-EPMC7539228 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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IMPAD1 and KDELR2 drive invasion and metastasis by enhancing Golgi-mediated secretion.

Bajaj Rakhee R Kundu Samrat T ST Grzeskowiak Caitlin L CL Fradette Jared J JJ Scott Kenneth L KL Creighton Chad J CJ Gibbons Don L DL

Oncogene 20200804 37

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 ...[more]

PMID: 32753652

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Dataset Information

IMPAD1 and KDELR2 drive invasion and metastasis by enhancing Golgi-mediated secretion.

Publications

IMPAD1 and KDELR2 drive invasion and metastasis by enhancing Golgi-mediated secretion.

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