SOSTDC1 inhibits bone metastasis in non-small cell lung cancer and may serve as a clinical therapeutic target

Int J Mol Med. 2018 Dec;42(6):3424-3436. doi: 10.3892/ijmm.2018.3926. Epub 2018 Oct 10.

Abstract

Bone metastasis occurs in ~40% patients with non‑small cell lung cancer (NSCLC), resulting in serious morbidity and mortality. Sclerostin domain‑containing protein 1 (SOSTDC1) has been demonstrated to be associated with the development and progression of multiple types of cancer. However, the role of SOSTDC1 in NSCLC bone metastasis remains unclear. In the present study, it was identified that SOSTDC1 was downregulated in NSCLC bone metastatic lesions compared with that in primary tumors, and low SOSTDC1 expression predicted poor prognosis for patients with NSCLC. Functionally, SOSTDC1 overexpression suppressed NSCLC cell proliferation, migration, invasion and cancer cell‑induced osteoclastogenesis, while SOSTDC1 knockdown produced the opposite effect. In addition, a number of potential downstream target genes of SOSTDC1, which were demonstrated to be associated with tumor progression and bone metastasis, were identified in NSCLC cells by RNA deep sequencing and RT‑qPCR assays. The results from the present study may provide useful insight for an improved understanding of the pathogenesis of NSCLC bone metastasis, and suggest that SOSTDC1 may be a potential prognostic biomarker and therapeutic target for NSCLC bone metastasis.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Bone Neoplasms / genetics
  • Bone Neoplasms / secondary*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Lung Neoplasms / pathology*
  • Male
  • Mice, Inbred C57BL
  • Middle Aged
  • Molecular Targeted Therapy*
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Osteoclasts / pathology
  • Osteogenesis
  • Prognosis
  • Proteins / genetics
  • Proteins / metabolism*
  • Survival Analysis

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • SOSTDC1 protein, human