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

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.

• Authors: Octavia Cadassou, Muhammad-Zawwad Raza, Christelle Machon, Laura Gudefin, Célia Armanet, Kamel Chettab, Jérôme Guitton, Maria Grazia Tozzi, Charles Dumontet, Emeline Cros-Perrial, Lars Petter Jordheim
• Journal: Cellular oncology (Dordrecht) (Cell Oncol (Dordr)) Vol. 44 Issue 1 Pg. 151-165 (Feb 2021) ISSN: 2211-3436 [Electronic] Netherlands
• PMID: 32970317 (Publication Type: Journal Article)

Chemical References

• Nucleotides
• RNA, Messenger
• Cyclooxygenase 2
• Proto-Oncogene Proteins c-akt
• 5'-Nucleotidase
• NT5C2 protein, human
• Adenosine
• Dinoprostone

Topics

• 5'-Nucleotidase (deficiency, metabolism)
• Adenosine (pharmacology)
• Animals
• Breast Neoplasms (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Cyclooxygenase 2 (metabolism)
• Dinoprostone (metabolism)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Lung Neoplasms (genetics, pathology)
• Mice
• Models, Biological
• Nucleotides (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Messenger (genetics, metabolism)
• Signal Transduction (drug effects)