Angio-associated migratory cell protein (AAMP) interacts with cell division cycle 42 (CDC42) and enhances migration and invasion in human non-small cell lung cancer cells

Cancer Lett. 2021 Apr 1;502:1-8. doi: 10.1016/j.canlet.2020.11.050. Epub 2020 Dec 3.

Abstract

Angio-associated migratory cell protein (AAMP) is considered a pro-tumor protein, which contributes to angiogenesis, proliferation, adhesion, and other biological activities. Although AAMP is known to facilitate the motility of breast cancer cells and smooth muscle cells by regulating ras homolog family member A (RHOA) activity, the function of AAMP in the metastasis of non-small cell lung cancer (NSCLC) cells still remains unknown. In the present study, AAMP was upregulated in non-small cell lung carcinoma, and was found to promote migration and invasion in NSCLC cells. Further experiments demonstrated that AAMP interacted with cell division cycle 42 (CDC42) and promoted its activation, resulting in the formation of cellular protrusions. Subsequently, we found that AAMP enhanced CDC42 activation by impairing the combination of rho GTPase activating protein 1 (ARHGAP1) and CDC42. Taken together, we revealed and elucidated the critical role of AAMP in the migration and invasion of NSCLC cells and presented a new potential target for lung cancer therapy.

Keywords: AAMP; ARHGAP1; CDC42; Invasion; Migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement
  • GTPase-Activating Proteins / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Neoplasm Invasiveness
  • Up-Regulation
  • cdc42 GTP-Binding Protein / metabolism*

Substances

  • AAMP protein, human
  • ARHGAP1 protein, human
  • Adaptor Proteins, Signal Transducing
  • GTPase-Activating Proteins
  • CDC42 protein, human
  • cdc42 GTP-Binding Protein