FAIM-S functions as a negative regulator of NF-κB pathway and blocks cell cycle progression in NSCLC cells

Cell Cycle. 2020 Dec;19(24):3458-3467. doi: 10.1080/15384101.2020.1843811. Epub 2020 Nov 29.

Abstract

Tumorigenesis is closely related to the disorder of the cell cycle. The cell cycle progression includes the interphase (G0/G1, S, and G2 phase) and mitosis (M phase). CCND1 is a key protein that regulates the entry of the G0/G1 phase into the S phase. In our study, we found that the short form of Fas Apoptosis Inhibitory Molecule 1 (FAIM-S) could regulate the expression of CCND1 and had a tumor-suppressing role in non-small cell lung cancer (NSCLC). Overexpressing FAIM-S significantly inhibited the proliferation and cell cycle progression in NSCLC cells. Further studies demonstrated that FAIM-S could interact with IKK-α, reducing its protein stability. This effect led to the suppression of the NF-κB pathway, resulting in the decreased expression of CCND1. Thus, our study demonstrated that FAIM-S functioned as a negative regulator of the NF-κB pathway and played a tumor-suppressing role through blocking cell cycle progression in NSCLC cells.

Keywords: CCND1; FAIM-S; NF-κB; cell cycle; non-small cell lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Cycle Checkpoints / genetics*
  • Cell Proliferation / genetics
  • Cyclin D1 / metabolism
  • Genes, Tumor Suppressor
  • Humans
  • I-kappa B Kinase / metabolism
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • NF-kappa B / metabolism*
  • Proteolysis
  • Signal Transduction / genetics*
  • Transfection

Substances

  • Apoptosis Regulatory Proteins
  • CCND1 protein, human
  • FAIM protein, human
  • NF-kappa B
  • Cyclin D1
  • CHUK protein, human
  • I-kappa B Kinase

Grants and funding

This work is supported by the National Natural Science Foundation of China (81902346) and the Natural Science Foundation of Jiangxi Province (20192BAB215038).