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

Rakhee Bajaj, Samrat T. Kundu, Caitlin L. Grzeskowiak, Jared J. Fradette, Kenneth L. Scott, Chad J. Creighton, Don L. Gibbons

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5979-5994
Number of pages16
JournalOncogene
Volume39
Issue number37
DOIs
StatePublished - Sep 10 2020

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

MD Anderson CCSG core facilities

  • Functional Genomics Core

Fingerprint

Dive into the research topics of 'IMPAD1 and KDELR2 drive invasion and metastasis by enhancing Golgi-mediated secretion'. Together they form a unique fingerprint.

Cite this