SASS6 promotes proliferation of esophageal squamous carcinoma cells by inhibiting the p53 signaling pathway

Carcinogenesis. 2021 Feb 25;42(2):254-262. doi: 10.1093/carcin/bgaa067.

Abstract

SASS6 encodes for the Homo sapiens SAS-6 centriolar assembly protein and is important for proper centrosome formation. Although centrosomes are amplified in a wide variety of tumor types, abnormally high SASS6 expression had previously only been identified in colon cancer. Moreover, the role of SASS6 in esophageal squamous cell carcinoma (ESCC) pathogenesis has not yet been elucidated. The aim of this study was to investigate the role and mechanisms of SASS6 in ESCC. In this study, we found that the mRNA and protein levels of SASS6 were increased in human ESCC samples. In addition, SASS6 protein expression was associated with the esophageal cancer stage and negatively affected survival of patients with ESCC. Furthermore, silencing of SASS6 inhibited cell growth and promoted apoptosis of ESCC cells in vitro and inhibited xenograft tumor formation in vivo. A genetic cluster and pathway analysis showed that SASS6 regulated the p53 signaling pathway. Western blot demonstrated that CCND2, GADD45A and EIF4EBP1 protein expression decreased and that TP53 protein expression increased after the knockdown of SASS6 in ESCC cells. Therefore, SASS6 promoted the proliferation of esophageal cancer by inhibiting the p53 signaling pathway. SASS6 has potential as a novel tumor marker and a therapeutic target for ESCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cyclin D2 / metabolism
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology*
  • Esophageal Neoplasms / surgery
  • Esophageal Squamous Cell Carcinoma / mortality
  • Esophageal Squamous Cell Carcinoma / pathology*
  • Esophageal Squamous Cell Carcinoma / surgery
  • Esophagectomy
  • Esophagus / pathology
  • Esophagus / surgery
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Mice
  • Middle Aged
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / metabolism*
  • Xenograft Model Antitumor Assays

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • CCND2 protein, human
  • Cell Cycle Proteins
  • Cyclin D2
  • EIF4EBP1 protein, human
  • GADD45A protein, human
  • SASS6 protein, human
  • TP53 protein, human
  • Tumor Suppressor Protein p53