Nme2, also known as Nucleoside Diphosphate Kinase 2, is multifunctional. It is involved in metastasis-suppression in multiple cancers and is associated with pathways like telomerase regulation [1,3,4]. In erythroid development, it has a role along with Nme1 as NDP kinases, and they are responsible for a majority of NDP kinase activity in mammals [2].

A double knockout Nme1/Nme2 mouse model showed that these genes are crucial for normal growth and survival. The knockout mice were stunted, died perinatally, and displayed hematologic phenotypes such as severe anemia and abnormal erythroid cell development, suggesting Nme2's role in erythropoiesis [2]. In a UV-induced melanoma mouse model, ablation of Nme2 enhanced metastatic activity, indicating its metastasis-suppressor function in vivo [4]. In gastric cancer cells, over-expression of Nme2 reduced proliferation, migration, and invasion, limiting metastasis [3].

In conclusion, Nme2 has important functions in metastasis-suppression, erythroid development, and regulation of cell behavior in cancer. The Nme1/Nme2 double knockout and other mouse models have revealed its significance in hematologic disorders and cancer, providing insights into potential therapeutic targets for related diseases.

References:

1. Kar, Anirban, Chowdhury, Shantanu. 2014. Inhibition of telomerase activity by NME2: impact on metastasis suppression? In Naunyn-Schmiedeberg's archives of pharmacology, 388, 235-41. doi:10.1007/s00210-014-1077-y. https://pubmed.ncbi.nlm.nih.gov/25547372/

2. Postel, Edith Horn, Zou, Xiaoming, Notterman, Daniel A, La Perle, Krista M D. 2009. Double knockout Nme1/Nme2 mouse model suggests a critical role for NDP kinases in erythroid development. In Molecular and cellular biochemistry, 329, 45-50. doi:10.1007/s11010-009-0110-9. https://pubmed.ncbi.nlm.nih.gov/19381783/

3. Liu, Yan-fei, Yang, Aijun, Liu, Wei, Dong, Jing-fei, Li, Min. 2015. NME2 reduces proliferation, migration and invasion of gastric cancer cells to limit metastasis. In PloS one, 10, e0115968. doi:10.1371/journal.pone.0115968. https://pubmed.ncbi.nlm.nih.gov/25700270/

4. Pamidimukkala, Nidhi, Puts, Gemma S, Kathryn Leonard, M, Merlino, Glenn, Kaetzel, David M. 2020. Nme1 and Nme2 genes exert metastasis-suppressor activities in a genetically engineered mouse model of UV-induced melanoma. In British journal of cancer, 124, 161-165. doi:10.1038/s41416-020-01096-w. https://pubmed.ncbi.nlm.nih.gov/33024267/