Phosphorylase kinase β affects colorectal cancer cell growth and represents a novel prognostic biomarker

J Cancer Res Clin Oncol. 2017 Jun;143(6):971-980. doi: 10.1007/s00432-017-2362-1. Epub 2017 Mar 8.

Abstract

Purpose: To study the expression and intracellular localization of phosphorylase kinase β (PHKβ) protein in colorectal cancers (CRCs), analyze its correlation with clinicopathological features and prognosis, and study the biological roles and mechanism-of-action of PHKβ in CRC cell lines.

Methods: Quantitative polymerase chain reaction (qPCR) and western blot assays were performed to compare the expressions of PHKβ mRNA and protein in CRC tissues and matched normal mucosa. Tissue microarrays and immunohistochemical staining were performed to detect the expression and intracellular location of PHKβ protein and analyze its correlation with the clinicopathological characteristics and prognosis in CRC patients. Proliferation, cell cycle, wound healing, and xenograft models were used to elucidate the potential role of PHKβ in vitro and in vivo.

Results: PHKβ mRNA and protein were found to be overexpressed in CRC tissue compared to the levels in normal mucosa. Positive expression of PHKβ was significantly correlated with TNM stage and distal metastasis, and elevated expression of PHKβ was an independent prognostic factor in patients with CRC. PHKβ knockdown impaired proliferation of CRC in vitro and in vivo and induced cell cycle arrest.

Conclusions: PHKβ affects CRC cell growth and represents a novel prognostic biomarker.

Keywords: Colorectal cancer; PHKβ; Prognosis, cell cycle; Proliferation.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / genetics
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Middle Aged
  • Phosphorylase Kinase / genetics
  • Phosphorylase Kinase / physiology*
  • Prognosis
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Phosphorylase Kinase