Survival of Head and Neck Cancer Cells Relies upon LZK Kinase-Mediated Stabilization of Mutant p53

Cancer Res. 2017 Sep 15;77(18):4961-4972. doi: 10.1158/0008-5472.CAN-17-0267. Epub 2017 Jul 31.


Head and neck squamous cell carcinoma (HNSCC) includes epithelial cancers of the oral and nasal cavity, larynx, and pharynx and accounts for ∼350,000 deaths per year worldwide. Smoking-related HNSCC is associated with few targetable mutations but is defined by frequent copy-number alteration, the most common of which is gain at 3q. Critical 3q target genes have not been conclusively determined for HNSCC. Here, we present data indicating that MAP3K13 (encoding LZK) is an amplified driver gene in HNSCC. Copy-number gain at 3q resulted in increased MAP3K13 mRNA in HNSCC tumor samples and cell lines. Silencing LZK reduced cell viability and proliferation of HNSCC cells with 3q gain but not control cell lines. Inducible silencing of LZK caused near-complete loss of colony-forming ability in cells harboring 3q gain. These results were validated in vivo by evidence that LZK silencing was sufficient to reduce tumor growth in a xenograft model of HNSCC. Our results establish LZK as critical for maintaining expression of mutant stabilized p53. Cancer Res; 77(18); 4961-72. ©2017 AACR.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers, Tumor
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Proliferation*
  • Female
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology*
  • Humans
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / metabolism*
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Mutant Proteins / chemistry
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism*
  • Mutation / genetics*
  • Protein Stability
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Xenograft Model Antitumor Assays


  • Biomarkers, Tumor
  • Mutant Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • MAP Kinase Kinase Kinases
  • MAP3K13 protein, human