Nme1 and Nme2 genes exert metastasis-suppressor activities in a genetically engineered mouse model of UV-induced melanoma

Nidhi Pamidimukkala; Gemma S Puts; M Kathryn Leonard; Devin Snyder; Sandrine Dabernat; Edward C De Fabo; Frances P Noonan; Andrzej Slominski; Glenn Merlino; David M Kaetzel

doi:10.1038/s41416-020-01096-w

Nme1 and Nme2 genes exert metastasis-suppressor activities in a genetically engineered mouse model of UV-induced melanoma

Br J Cancer. 2021 Jan;124(1):161-165. doi: 10.1038/s41416-020-01096-w. Epub 2020 Oct 7.

Authors

Nidhi Pamidimukkala^#¹, Gemma S Puts^#¹, M Kathryn Leonard^{1

2}, Devin Snyder¹, Sandrine Dabernat³, Edward C De Fabo⁴, Frances P Noonan⁴, Andrzej Slominski⁵, Glenn Merlino⁶, David M Kaetzel^{7

8

9}

Affiliations

¹ Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland-Baltimore, Baltimore, MD, USA.
² American Association for Cancer Research, Philadelphia, PA, USA.
³ INSERM U1035, Université de Bordeaux, Bordeaux, France.
⁴ The George Washington University Medical Center, Washington, DC, USA.
⁵ Departments of Dermatology and Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
⁶ Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
⁷ Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland-Baltimore, Baltimore, MD, USA. DKaetzel@som.umaryland.edu.
⁸ Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland-Baltimore, Baltimore, MD, USA. DKaetzel@som.umaryland.edu.
⁹ Research and Development Service, VA Maryland Health Care System, Baltimore, MD, USA. DKaetzel@som.umaryland.edu.

^# Contributed equally.

Abstract

NME1 is a metastasis-suppressor gene (MSG), capable of suppressing metastatic activity in cell lines of melanoma, breast carcinoma and other cancer origins without affecting their growth in culture or as primary tumours. Herein, we selectively ablated the tandemly arranged Nme1 and Nme2 genes to assess their individual impacts on metastatic activity in a mouse model (HGF:p16^-/-) of ultraviolet radiation (UVR)-induced melanoma. Metastatic activity was strongly enhanced in both genders of Nme1- and Nme2-null mice, with stronger activity in females across all genotypes. The study ascribes MSG activity to Nme2 for the first time in an in vivo model of spontaneous cancer, as well as a novel metastasis-suppressor function to Nme1 in the specific context of UVR-induced melanoma.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Disease Models, Animal
Female
Genes, Tumor Suppressor*
Male
Melanoma / genetics*
Melanoma / pathology*
Mice
Mice, Inbred C57BL
Mice, Knockout
NM23 Nucleoside Diphosphate Kinases / genetics*
Ultraviolet Rays / adverse effects

Substances

NM23 Nucleoside Diphosphate Kinases
Nme1 protein, mouse
Nme2 protein, mouse

Abstract

Publication types

MeSH terms

Substances

Grants and funding