ALPK1 Expression Is Associated with Lymph Node Metastasis and Tumor Growth in Oral Squamous Cell Carcinoma Patients

Am J Pathol. 2019 Jan;189(1):190-199. doi: 10.1016/j.ajpath.2018.09.003. Epub 2018 Oct 11.


Oral squamous cell carcinoma (OSCC) is the most common malignant cancer, with high mortality rates in advanced stages. Recent studies have shown that the expression of ALPK1 mRNA and its inhibitory differentiation function are associated with cancer progression. However, the expression and clinicopathologic features of ALPK1 in OSCC remain unexplored. Herein, the authors investigated the expression patterns of ALPK1 in 39 matched OSCC patients and examined the relationship between ALPK1 protein expression and clinicopathologic factors using immunohistochemical scores. Using Western blot analysis, ALPK1 expression was found to be significantly higher in tumor tissues than that in nontumor tissues. Through an immunoreactive scoring system, a significantly higher number of advanced-stage tumor size T4 and lymph node metastasis N2 exhibited higher ALPK1 expression levels than that exhibited by T1/T2/T3 tumors and N0/N1. In addition, ALPK1 protein expression was aberrant in malignant oral cancer cell lines compared with that in pre-malignant oral epithelial cells, whereas minimal expression was observed in normal oral epithelial cells. Knockdown of ALPK1 resulted in a significant reduction in cell growth, migration, and invasion capacity in vitro. Consequently, expression of N-cadherin and vimentin decreased in ALPK1-deficient cells. Thus, these results suggest that ALPK1 serves as a potential biomarker and target for OSCC development in late stages.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / immunology
  • Cadherins / genetics
  • Cadherins / immunology
  • Cadherins / metabolism
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • Keratinocytes / immunology
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / immunology
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology
  • Neoplasm Staging
  • Protein Kinases / biosynthesis*
  • Protein Kinases / genetics
  • Protein Kinases / immunology
  • Tongue Neoplasms / enzymology*
  • Tongue Neoplasms / genetics
  • Tongue Neoplasms / immunology
  • Tongue Neoplasms / pathology
  • Vimentin / genetics
  • Vimentin / immunology
  • Vimentin / metabolism


  • Antigens, CD
  • Biomarkers, Tumor
  • CDH2 protein, human
  • Cadherins
  • Neoplasm Proteins
  • VIM protein, human
  • Vimentin
  • Protein Kinases
  • ALPK1 protein, human