Id-1 promotes migration and invasion of non-small cell lung cancer cells through activating NF-κB signaling pathway

J Biomed Sci. 2017 Dec 12;24(1):95. doi: 10.1186/s12929-017-0400-6.

Abstract

Background: Numerous studies have shown that Id-1 (Inhibitor of differentiation 1) is upregulated in several cancers and associated with tumor malignant characters. However, the clinical significance and biological role of Id-1 in non-small cell lung cancer (NSCLC) remains unclear.

Methods: We used RT-PCR, Western blot and Immunohistochemistry to measure Id-1 expression in NSCLC tissues and matched adjacent noncancerous tissues. The expression pattern of Id-1 in NSCLC tissues was determined by scoring system of immunohistochemical analysis. The Kaplan-Meier method was used to calculate the survival curve, and log-rank test to determine statistical significance. The Id-1 gene was overexpressed or downreuglated with Lentiviral vectors in NSCLC cells. And, the migration ability of NSCLC cells was tested in a Transwell Boyden Chamber.

Results: We found that Id-1 is generally expressed higher in NSCLC tissues compared with matched adjacent noncancerous tissues. We also found that high Id-1 expression in tumor tissues is significantly correlated with tumor progression and poor survival in NSCLC patients. Furthermore, our experimental data revealed that knockdown of Id-1 significantly suppressed the proliferation, migration and invasion of NSCLC cells, whereas ectopic expression of Id-1 promoted the malignant phenotype of NSCLC cells. Mechanistic study showed that NF-κB signaling pathway contributed to the effects of Id-1 in NSCLC cells. Moreover, blocking the NF-κB pathway significantly inhibited the tumor-promoting actions of Id-1 in NSCLC cells.

Conclusions: We identified a tumorigenic role of Id-1 in NSCLC and provided a novel therapeutic target for NSCLC patients.

Keywords: Id-1; Invasion; Migration; NF-κB signaling pathway; Non-small cell lung cancer.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Inhibitor of Differentiation Protein 1 / genetics*
  • Inhibitor of Differentiation Protein 1 / metabolism
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Signal Transduction

Substances

  • ID1 protein, human
  • Inhibitor of Differentiation Protein 1
  • NF-kappa B