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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:44

Enthalten in:

Cellular oncology (Dordrecht) - 44(2021), 1 vom: 24. Feb., Seite 151-165

Sprache:

Englisch

Beteiligte Personen:

Cadassou, Octavia [VerfasserIn]
Raza, Muhammad-Zawwad [VerfasserIn]
Machon, Christelle [VerfasserIn]
Gudefin, Laura [VerfasserIn]
Armanet, Célia [VerfasserIn]
Chettab, Kamel [VerfasserIn]
Guitton, Jérôme [VerfasserIn]
Tozzi, Maria Grazia [VerfasserIn]
Dumontet, Charles [VerfasserIn]
Cros-Perrial, Emeline [VerfasserIn]
Jordheim, Lars Petter [VerfasserIn]

Links:

Volltext

Themen:

5'-Nucleotidase
Adenosine
Breast cancer
CD73
CN-II
COX-2
Cancer cell biology
Cyclooxygenase 2
Dinoprostone
EC 1.14.99.1
EC 2.7.11.1
EC 3.1.3.5
Journal Article
K72T3FS567
K7Q1JQR04M
Lung cancer
NT5C2 protein, human
Nucleotides
Proto-Oncogene Proteins c-akt
RNA, Messenger

Anmerkungen:

Date Completed 23.09.2021

Date Revised 23.09.2021

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s13402-020-00558-w

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM315411473