CK2α′ drives lung cancer metastasis by targeting BRMS1 nuclear export and degradation Journal Article

   


Authors: Liu, Y.; Amin, E. B.; Mayo, M. W.; Chudgar, N. P.; Bucciarelli, P. R.; Kadota, K.; Adusumilli, P. S.; Jones, D. R.
Article Title: CK2α′ drives lung cancer metastasis by targeting BRMS1 nuclear export and degradation
Abstract: 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. © 2016 American Association for Cancer Research.
Journal Title: Cancer Research
Volume: 76
Issue: 9
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2016-05-01
Start Page: 2675
End Page: 2686
Language: English
DOI: 10.1158/0008-5472.can-15-2888
PROVIDER: scopus
PMCID: PMC4873401
PUBMED: 26980766
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-84969560179&partnerID=40&md5=b6af204d2ad7056d131000b50d625938
Notes: Article -- Export Date: 2 June 2016 -- Source: Scopus
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MSK Authors
  1. Kyuichi Kadota
    85 Kadota
  2. Prasad S Adusumilli
    496 Adusumilli
  3. Elianna Binte Mohamed Amin
    10 Mohamed Amin
  4. David Randolph Jones
    417 Jones
  5. Yuan Liu
    22 Liu
  6. Neel Pankaj Chudgar
    15 Chudgar
  7. Peter Ryan Bucciarelli
    4 Bucciarelli
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