The mitochondrially-localized nucleoside diphosphate kinase D (NME4) is a novel metastasis suppressor.

ABSTRACT:

Background

Mitochondrial nucleoside diphosphate kinase (NDPK-D, NME4, NM23-H4) is a multifunctional enzyme mainly localized in the intermembrane space, bound to the inner membrane.

Results

We constructed loss-of-function mutants of NDPK-D, lacking either NDP kinase activity or membrane interaction and expressed mutants or wild-type protein in cancer cells. In a complementary approach, we performed depletion of NDPK-D by RNA interference. Both loss-of-function mutations and NDPK-D depletion promoted epithelial-mesenchymal transition and increased migratory and invasive potential. Immunocompromised mice developed more metastases when injected with cells expressing mutant NDPK-D as compared to wild-type. This metastatic reprogramming is a consequence of mitochondrial alteration

SUBMITTER: Lacombe ML 

PROVIDER: S-EPMC8529772 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature