KLK4 silencing inhibits the growth of oral squamous cell carcinoma through Wnt/β-catenin signaling pathway

Cell Biol Int. 2017 Apr;41(4):392-404. doi: 10.1002/cbin.10736. Epub 2017 Feb 16.

Abstract

Oral squamous cell carcinoma (OSCC) is a malignancy that largely impacts the quality of people's daily life. Kallikrein-related peptidase 4 (KLK4) is highly expressed in OSCC; however, its roles in OSCC cells are unclear. In the present study, the effect of KLK4 silencing on the growth of OSCC cells was investigated. Our study showed that the proliferation and colony formation of OSCC cells was inhibited by KLK4 silencing and their cell cycle was arrested. Additionally, apoptosis of OSCC cells was enhanced by KLK4 silencing, with increased protein levels of cleaved PARP, cleaved caspase-3, Bax and decreased levels of Bcl-2. KLK4 silencing inhibited the Wnt/β-catenin signaling pathway, as evidence by decreased protein levels of Wnt1, β-catenin, reduced GSK-3β phosphorylation as well as decreased levels of cyclinD1 and c-myc proteins. We further showed that Wnt/β-catenin activator reversed the effects of KLK4 silencing on the proliferation and apoptosis of OSCC cells. We concluded that KLK4 silencing inhibited the growth of OSCC cells through Wnt/β-catenin signaling pathway, suggesting that KLK4 may become a promising therapeutic target for the treatment of OSCC.

Keywords: Wnt/β-catenin; apoptosis; cell cycle; kallikrein-related peptidase 4; oral squamous cell carcinoma; proliferation.

MeSH terms

  • Apoptosis
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin D1 / metabolism
  • Humans
  • Kallikreins / genetics*
  • Kallikreins / metabolism
  • Mouth Neoplasms / enzymology*
  • Mouth Neoplasms / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Wnt Signaling Pathway*

Substances

  • CCND1 protein, human
  • MYC protein, human
  • Proliferating Cell Nuclear Antigen
  • Proto-Oncogene Proteins c-myc
  • RNA, Small Interfering
  • Cyclin D1
  • Kallikreins
  • kallikrein 4