Whereas most genetic alterations of primary tumours remain unchanged in metastases, expression of the cell adhesion molecule Ep-CAM and of nm23 is more frequently reduced than increased in metastases, compared with their primary tumours, suggesting relevance to the process of metastasis.
When studying Bgl II RFLPs, allelic losses of the nm23 gene were found in 3/12 (25%) informative tumors, and all 3 had lymph node and/or distant metastases.
Western blot analysis revealed that the expression levels of beta-catenin, c-Myc, and cyclin D1 were upregulated, but Dkk-1 and nm23 were dramatically downregulated in M-H7402 cells, which suggests that the 2 cell lines were remarkably different in molecular events associated with metastasis.
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.
We hypothesize that the mechanism of action of Nm23 in metastasis suppression involves diminished signal transduction downstream of a particular receptor.
We have employed a transgenic mouse strain harboring a tandem deletion of the nm23-m1 and nm23-m2 genes to assess the combined contribution of these genes to suppression of melanoma metastasis.
We have employed a site-directed mutagenesis approach to demonstrate that the 3'-5' exonuclease activity of NM23-H1 is required for its metastasis suppressor function.
We have analyzed expression of nm23 polypeptide in acquired melanocytic nevi (n = 19), dysplastic nevi (n = 19), malignant melanomas (n = 22) and metastases of malignant melanomas (n = 47) in situ.
We evaluated the association of genetic polymorphisms of metastasis suppressor gene NME1 with breast cancer prognosis in a follow-up study of patients with primary breast cancer and further investigated the functions of these polymorphisms.
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.
We describe a serine phosphorylation of the putative metastasis suppressor protein Nm23, and present evidence of its relevance to the signal transduction and tumor metastatic processes.
We demonstrate that 1) FGFR1 endocytosis is defective in the VHL mutant and is rescued by reexpression of wild-type VHL, 2) VHL is recruited to FGFR1-containing, but not EGFR-containing, endosomal vesicles, 3) VHL exhibits a functional relationship with Rab5a and dynamin 2 in FGFR1 internalization, and 4) the endocytic function of VHL is mediated through the metastasis suppressor Nm23, a protein known to regulate dynamin-dependent endocytosis.
We also described the current understanding of the cellular and viral interactions of Nm23-H1 and their reference to transcription regulation and metastasis.
Upon mammary fat pad or subcutaneous injection into nude mice, both the nm23-H1 and control transfected lines produced primary tumors; however, the nm23-H1-transfected lines produced metastases in significantly fewer mice than did control transfected lines.
Two-dimensional gel electrophoresis and liquid chromatography-tandem mass spectrometry were performed to investigate the influence of human nonmetastatic clone 23 type 1 (nm23-H1), a metastasis-associated gene on proteomic alterations in cancer cells of the uterine cervix.
Twenty-eight cell lines derived from renal primary tumors and 8 cell lines derived from metastatic tumors expressed both the Nm23-H1 and Nm23-H2 proteins.