Enhanced migration of breast and lung cancer cells deficient for cN-II and CD73 via COX-2/PGE2/AKT axis regulation

Lung Cancer
25/09/2020

Cell Oncol (Dordr). 2020 Sep 24. doi: 10.1007/s13402-020-00558-w. Online ahead of print.

ABSTRACT

PURPOSE: Purine metabolism involves various intracellular and extracellular enzymes, including cN-II and CD73 that dephosphorylate intracellular and extracellular nucleoside monophosphates into their corresponding nucleosides. We conducted a study to better understand the biological roles of these enzymes in breast and lung cancer cells.

METHODS: We modified cN-II and/or CD73 expression in human breast cancer cells (MDA-MB-231), human lung cancer cells (NCI-H292) and murine breast cancer cells (4T1) using the CRISPR/Cas9 technique, and evaluated their impact on various cellular parameters such as proliferation, migration, invasion, intracellular nucleotide pools and nucleotide metabolism-related gene expression under extracellular nucleotide stress conditions.

RESULTS: Intracellular nucleotide contents were found to be altered in the modified cancer cell models both at their basal levels and after exposure to adenosine or AMP. Altered cN-II and CD73 levels were also found to be associated with cell migration and invasion alterations, involving TIMP-2, MMP-2 and MMP-9 expression, as well as alterations in the COX-2/PGE2/AKT pathway.

CONCLUSION: Our results highlight new cell-specific roles of cN-II and CD73 in cancer cell biology and provide insight into their interactions with different intracellular pathways.