CK2α' Drives Lung Cancer Metastasis by Targeting BRMS1 Nuclear Export and Degradation. Academic Article uri icon

Overview

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. Cancer Res; 76(9); 2675-86. ©2016 AACR.

publication date

  • March 15, 2016

Research

keywords

  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Neoplasm Invasiveness
  • Repressor Proteins

Identity

PubMed Central ID

  • PMC4873401

Scopus Document Identifier

  • 84969560179

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-15-2888

PubMed ID

  • 26980766

Additional Document Info

volume

  • 76

issue

  • 9