SHCBP1 is a novel target and exhibits tumor‑promoting effects in gastric cancer

Oncol Rep. 2019 Mar;41(3):1649-1657. doi: 10.3892/or.2018.6952. Epub 2018 Dec 21.

Abstract

The present study investigated the expression and potential influence of SHC SH2 domain‑binding protein 1 (SHCBP1) in gastric cancer (GC) cells. SHCBP1 is closely related to cell proliferation and cell cycle progression, but its role in GC remains unclear. The TCGA database revealed that SHCBP1 is highly expressed in GC tissues. Furthermore, SHCBP1 was revealed to be highly expressed in GC cell lines MGC‑803 and SGC‑7901 cells, and downregulation of SHCBP1 significantly inhibited GC cell proliferation. Furthermore, SHCBP1 expression promoted cell cycle progression and inhibition of apoptosis. Since the CDK4, cyclin D1 and caspase family proteins play important roles in cell cycle and apoptosis regulation, it was examined whether there was an association between SHCBP1 and these signaling pathways in GC. Our results revealed that SHCBP1 promoted cell cycle progression by regulating the CDK4‑cyclin D1 cascade and suppressed caspase‑3, caspase PARP‑dependent apoptotic pathways. Cell invasion and metastasis experiments also revealed that SHCBP1 promoted tumor growth and invasiveness. These tumor‑promoting functions of SHCBP1 may provide a potential molecular basis for the diagnosis and targeted therapy of GC.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Caspase 3 / metabolism
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 4 / metabolism
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • RNA, Small Interfering / metabolism
  • Shc Signaling Adaptor Proteins / genetics
  • Shc Signaling Adaptor Proteins / metabolism*
  • Signal Transduction
  • Stomach / pathology
  • Stomach Neoplasms / diagnosis
  • Stomach Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • CCND1 protein, human
  • RNA, Small Interfering
  • SHCBP1 protein, human
  • Shc Signaling Adaptor Proteins
  • Cyclin D1
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • CASP3 protein, human
  • Caspase 3