Epithelial-to-mesenchymal transition drives a pro-metastatic Golgi compaction process through scaffolding protein PAQR11

Xiaochao Tan, Priyam Banerjee, Hou Fu Guo, Stephen Ireland, Daniela Pankova, Young Ho Ahn, Irodotos Michail Nikolaidis, Xin Liu, Yanbin Zhao, Yongming Xue, Alan R. Burns, Jonathon Roybal, Don L. Gibbons, Tomasz Zal, Chad J. Creighton, Daniel Ungar, Yanzhuang Wang, Jonathan M. Kurie

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Tumor cells gain metastatic capacity through a Golgi phosphoprotein 3-dependent (GOLPH3-dependent) Golgi membrane dispersal process that drives the budding and transport of secretory vesicles. Whether Golgi dispersal underlies the prometastatic vesicular trafficking that is associated with epithelial-to-mesenchymal transition (EMT) remains unclear. Here, we have shown that, rather than causing Golgi dispersal, EMT led to the formation of compact Golgi organelles with improved ribbon linking and cisternal stacking. Ectopic expression of the EMT-activating transcription factor ZEB1 stimulated Golgi compaction and relieved microRNA-mediated repression of the Golgi scaffolding protein PAQR11. Depletion of PAQR11 dispersed Golgi organelles and impaired anterograde vesicle transport to the plasma membrane as well as retrograde vesicle tethering to the Golgi. The N-terminal scaffolding domain of PAQR11 was associated with key regulators of Golgi compaction and vesicle transport in pull-down assays and was required to reconstitute Golgi compaction in PAQR11-deficient tumor cells. Finally, high PAQR11 levels were correlated with EMT and shorter survival in human cancers, and PAQR11 was found to be essential for tumor cell migration and metastasis in EMT-driven lung adenocarcinoma models. We conclude that EMT initiates a PAQR11-mediated Golgi compaction process that drives metastasis.

Original languageEnglish
Pages (from-to)117-131
Number of pages15
JournalJournal of Clinical Investigation
Issue number1
StatePublished - Jan 3 2017

Bibliographical note

Funding Information:
We thank Yiqun Zhang, Bih-Fang Pan, and Xiaoyan Zhang for technical assistance. This work was supported by the NIH through R01 CA181184 (to JMK), R01 CA125123 (to CJC), GM087364 (to YW), GM105920 (to YW), GM112786P30 (to YW), EY007551 (to ARB), K08 CA151661 (to DLG), NRF-2010-0027945 (to YHA), and MD Anderson Cancer Center Support Grant CA016672; by the American Cancer Society through RGS-09-278-01-CSM (to YW); by Cancer Prevention Research Institute of Texas (CPRIT) Multi-investigator Research Award RP120713 (to JMK, CJC, and DLG); and by MCubed and the Fastforward Protein Folding Disease Initiative of the University of Michigan (to YW). JMK holds the Elza A. and Ina S. Freeman Endowed Professorship in Lung Cancer. DLG is an R. Lee Clark Fellow of The University of Texas MD Anderson Cancer Center supported by the Jeane F. Shelby Scholarship Fund. MD Anderson's Proteomics and Metabolomics Facility is supported by MD Anderson Cancer Center, NIH High-End Instrumentation Program grant 1S10OD012304-0

ASJC Scopus subject areas

  • General Medicine


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