We developed a competitive permeable peptide (CPP) to impair the formation of the Nm23-H1/h-Prune complex and demonstrated that CPP causes impairment of cell motility, substantial impairment of tumor growth and metastases formation.
The cell-permeable (CP)-NM23 inhibited metastasis-associated phenotypes in tumor cell lines, blocked the establishment of lung metastases, and cleared already established pulmonary metastases, significantly prolonging the survival of tumor-bearing animals.
Thujone administration downregulated the expression of matrix metalloproteinase (MMP)-2, MMP-9, extracellular signal-regulated kinase (ERK)-1, ERK-2, and vascular endothelial growth factor (VEGF) and also upregulated the expression of nm-23, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 in the lung tissue of metastasis-induced animals.
Evidence for a metastasis suppressor function of NME1 in vivo comes from crossing NME1 (-/-) mice with mice prone to develop hepatocellular carcinoma; the double transgenic mice present a higher incidence of lung metastases.
Our findings suggest a correlation between high levels of NM23-H1 protein in the cytoplasm of the cells and progression of prostate cancer to metastasis, thus definitively identifying NM23-H1 as a new negative prognostic marker in prostate cancer.
Human nonmetastatic clone 23 Type 1 (nm23-H1) is demonstrated to have diverse roles in metastasis and survival for many cancers, which are probably caused via different impacts on its downstream genes.
To analyze the prognostic significance of the genes casein kinase 2 alpha subunit (CSNK2A1), anti-apoptosis clone-11 (AAC-11), and tumor metastasis suppressor NME1 in completely resected non-small cell lung cancer (NSCLC) patients.
We thus provide evidence that the loss of Nm23-H1, an event suspected to promote metastasis, may additionally function at an earlier stage of tumor development to drive the acquisition of chromosomal instability.