STK33 overexpression in hypopharyngeal squamous cell carcinoma: possible role in tumorigenesis

BMC Cancer. 2015 Jan 21:15:13. doi: 10.1186/s12885-015-1009-3.

Abstract

Background: The role of serine/threonine kinase 33 (STK33) gene in tumorigenesis is still controversial. This study was aimed to investigate whether STK33 had the effect on hypopharyngeal squamous cell carcinoma (HSCC) and relevant genes, as well as the potential relation to ERK1/2 pathway.

Methods: Immunohistochemistry was performed to investigate STK33 expression in human HSCC specimens. MTT, immunofluorescence, clone formation and matrigel invasion assays were employed to detect the effects of STK33 knockdown (STK33-RNAi) and/or PD98059 on major oncogenic properties of a HSCC cell line (Fadu), while, real-time PCR and western blot were used to examine the expressions of relevant genes.

Results: STK33 was over-expressed in HSCC specimens, which was significantly associated with certain clinicopathological parameters. STK33-RNAi in Fadu cells resulted in inhibition of proliferation, induction of apoptosis, reduction of clone formation, and decline in the migration and invasion. These effects were potentiated by administration of PD98059. Mechanistic studies revealed that STK33-RNAi led to an increase in Caspse-3, Nm-23-H1 and E-Cadherin expressions and a reduction in Bcl-2, Ki-67 and Vimentin expressions. Moreover, PD98059 significantly reduced both ERK1/2 and STK33 expressions in Fadu cells.

Conclusions: STK33 is a potential oncogene and a promising diagnostic marker for HSCC. STK33 may promote tumorigenesis and progression of HSCC, and serve as a valuable molecular target for treatment of HSCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Flavonoids / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Hypopharyngeal Neoplasms / metabolism*
  • Hypopharyngeal Neoplasms / pathology
  • Protein Serine-Threonine Kinases / metabolism*
  • Up-Regulation

Substances

  • Flavonoids
  • Protein Serine-Threonine Kinases
  • STK33 protein, human
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one