Sam68 promotes cellular proliferation and predicts poor prognosis in esophageal squamous cell carcinoma

Tumour Biol. 2015 Nov;36(11):8735-45. doi: 10.1007/s13277-015-3631-8. Epub 2015 Jun 7.

Abstract

Sam68 (Src-associated in mitosis of 68 kD) is a KH domain RNA-binding protein. The expression of Sam68 was correlated with kinds of tumors. Yet, the expression mechanisms and physiological significance of Sam68 in ESCC remains unclear. In this study, we clarified a potential role of Sam68 in the treatment of ESCC. Western blot and immunohistochemistry (IHC) analysis revealed that the protein level of Sam68 was higher in ESCC tumor tissues and cell lines. In addition, IHC stain revealed that Sam68 was positively correlated with clinical pathologic variables such as tumor grade and tumor invasion. In addition, Sam68 could be an independent prognostic indicator for patients' overall survival. In vitro studies such as starvation and refeeding assay along with Sam68-shRNA transfection assay demonstrated that Sam68 expression promoted proliferation of ESCC cells. And Sam68 downregulation caused decreased rate of cell growth and colony formation. Reasons are associated with growth arrest of cell cycle at G1/S phase. Moreover, our results clarified that Sam68 could promote ESCC cell proliferation via the activation of Akt/GSK-3β pathway. This research indicated that Sam68 might accelerate the cell cycle progression and be considered as a new therapy target in ESCC.

Keywords: Esophageal squamous cell carcinoma (ESCC); Prognosis; Proliferation; Sam68.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Adaptor Proteins, Signal Transducing / genetics*
  • Aged
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Esophageal Squamous Cell Carcinoma
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 / genetics
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Oncogene Protein v-akt / genetics
  • Prognosis
  • RNA-Binding Proteins / biosynthesis
  • RNA-Binding Proteins / genetics*
  • Signal Transduction

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • KHDRBS1 protein, human
  • RNA-Binding Proteins
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Oncogene Protein v-akt
  • Glycogen Synthase Kinase 3