CCDC85B promotes non-small cell lung cancer cell proliferation and invasion

Mol Carcinog. 2019 Jan;58(1):126-134. doi: 10.1002/mc.22914. Epub 2018 Oct 9.

Abstract

Coiled-coil domain containing 85 B (CCDC85B) is involved in diverse biological processes; however, its expression patterns and functions in human cancers are yet unknown. The present study demonstrated that the expression of CCDC85B in the cytoplasm of the non-small cell lung cancer (NSCLC) tumor cells was significantly higher compared to adjacent normal lung tissues (P < 0.05). Furthermore, CCDC85B expression correlated with advanced TNM stage (P = 0.004) and positive regional lymph node metastasis (P = 0.009) of NSCLC. In addition, in A549 and H1299 lung cancer cell lines, the overexpression of CCDC85B promoted cell proliferation and invasion, while siRNA-mediated CCDC85B knockdown exhibited opposite effects. CCDC85B promoted AKT and GSK3β phosphorylation and upregulated the levels of active β-catenin, Wnt targets c-myc, cyclin D1, and MMP7. Besides, the CCDC85B-induced upregulation of phosphorylated GSK3β and active β-catenin was rescued following the treatment with PI3 K inhibitor, LY294002. In conclusion, CCDC85B was associated with NSCLC progression as it promoted the proliferation and invasion of lung cancer cells through activated AKT/GSK3β/β-catenin oncogenic signaling pathway. Therefore, CCDC85B might serve as a novel target for NSCLC treatment.

Keywords: CCDC85B; invasion; non-small cell lung cancer; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary*
  • Apoptosis
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Large Cell / metabolism
  • Carcinoma, Large Cell / secondary*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / secondary*
  • Case-Control Studies
  • Cell Proliferation*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Repressor Proteins / metabolism*
  • Signal Transduction
  • Tumor Cells, Cultured

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • CCDC85B protein, human
  • Repressor Proteins