Angio-associated migratory cell protein interacts with epidermal growth factor receptor and enhances proliferation and drug resistance in human non-small cell lung cancer cells

Cell Signal. 2019 Sep;61:10-19. doi: 10.1016/j.cellsig.2019.05.004. Epub 2019 May 7.

Abstract

Angio-associated migratory cell protein (AAMP) is expressed in some human cancer cells. Previous studies have shown AAMP high expression predicted poor prognosis. But its biological role in non-small cell lung cancer (NSCLC) cells is still unknown. In our present study, we attempted to explore the functions of AAMP in NSCLC cells. According to our findings, AAMP knockdown inhibited lung cancer cell proliferation and inhibited lung cancer cell tumorigenesis in the mouse xenograft model. Epidermal growth factor receptor (EGFR) is a primary receptor tyrosine kinase (RTK) that promotes proliferation and plays an important role in cancer pathology. We found AAMP interacted with EGFR and enhanced its dimerization and phosphorylation at tyrosine 1173 which activated ERK1/2 in NSCLC cells. In addition, we showed AAMP conferred the lung cancer cells resistance to chemotherapeutic agents such as icotinib and doxorubicin. Taken together, our data indicate that loss of AAMP from NSCLC inhibits tumor growth and elevates drug sensitivity, and these findings have clinical implications to treat NSCLC cancers.

Keywords: AAMP; Doxorubicin; EGFR; Icotinib; Proliferation; Tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis / drug effects
  • Carcinogenesis / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation / genetics*
  • Crown Ethers / pharmacology
  • Dimerization
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / metabolism
  • Female
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Heterografts
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Mice
  • Phosphorylation / genetics
  • Quinazolines / pharmacology
  • Transfection
  • Tumor Burden / genetics

Substances

  • AAMP protein, human
  • Adaptor Proteins, Signal Transducing
  • Crown Ethers
  • Quinazolines
  • icotinib
  • EGFR protein, human
  • ErbB Receptors