We extended our analyses to colon cancer cell lines and found that knocking down Dyn1, besides to raise Nme1 extracellular amount, downregulates expression of molecular components that play key roles in tumour invasion.
Inhibition of the interactions between h-prune and GSK-3beta and nm23-H1 additively suppresses the migration of colon cancer and breast cancer cells, thus suggesting that h-prune regulates cell motility by two different means of action: through its PDE activity and in its interactions with protein partners.
We transfected nm23-H1 cDNA into the human colon cancer cell line, HT-29, to test the effects and cellular biological mechanism of nm23 protein in colon cancer.
Furthermore, loss of heterozygosity (LOH) at NM23.H1 locus was tested, 17/34 (50%) pancreatic tumors and 6/23 (26%) colon cancers showed mutations in codon 12 of K-ras; allelic loss of NM23.
For example, both the RB gene of retinoblastoma and the p53 gene, which is commonly mutated in breast and colon cancer among others, produce proteins involved in distinct steps of cell cycle control, while the nm23 product prevents metastasis.
This study was designed to reconcile our previous findings with the recent report of nm23-H1 allelic deletion in human colon cancers associated with poor prognosis.
A strong association has been observed between reduced expression of Nm23 gene and acquisition of metastatic behaviour in some tumour cells including breast cancer and melanoma, but not in others such as colon cancer, neuroblastoma, and cervical cancer.