CK2α′ drives lung cancer metastasis by targeting brms1 nuclear export and degradation

Yuan Liu, Elianna B. Amin, Marty W. Mayo, Neel P. Chudgar, Peter R. Bucciarelli, Kyuichi Kadota, Prasad S. Adusumilli, David R. Jones

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Breast cancer metastasis suppressor 1 (BRMS1) is decreased in non-small cell lung cancer (NSCLC) and other solid tumors, and its loss correlates with increased metastases. We show that BRMS1 is posttranslationally regulated by TNF-induced casein kinase 2 catalytic subunit (CK2α′) phosphorylation of nuclear BRMS1 on serine 30 (S30), resulting in 14-3-3ϵ-mediated nuclear exportation, increased BRMS1 cytosolic expression, and ubiquitin-proteasome-induced BRMS1 degradation. Using our in vivo orthotopic mouse model of lung cancer metastases, we found that mutation of S30 in BRMS1 or the use of the CK2- specific small-molecule inhibitor CX4945 abrogates CK2α′- induced cell migration and invasion and decreases NSCLC metastasis by 60-fold. Analysis of 160 human NSCLC specimens confirmed that tumor CK2α′ and cytoplasmic BRMS1 expression levels are associated with increased tumor recurrence, metastatic foci, and reduced disease-free survival. Collectively, we identify a therapeutically exploitable posttranslational mechanism by which CK2α-mediated degradation of BRMS1 promotes metastases in lung cancer.

Original languageEnglish (US)
Pages (from-to)2675-2686
Number of pages12
JournalCancer research
Issue number9
StatePublished - May 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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