miR-21 has also been shown to inhibit the expression of multiple metastasis suppressors [49], [50].
Although this has represented a 'kiss of death' to editors and study sections, emerging evidence from multiple metastasis-suppressor genes suggests that it may represent a strength, because it supports the hypothesis that these genes 'work' by a different mechanism.
Indeed, the ER gene has been shown to be a growth and/or metastasis suppressor in multiple cell types, and the negative effect of oestrogen on haematopoiesis suggests that this is also the case in leukaemias [ 15].
Although multiple pathways, including Wnt/ β-catenin and metastasis suppressor RKIP, likely mediates the anti-tumor activity of miR-101, the most important molecule could be EZH2, a histone-lysine N-methyltransferase that is heavily involved in cancer progression.
While NM23 proteins participate in multiple cellular regulatory pathways, mechanism(s) underlying the metastasis suppressor activity of NM23-H1/M1 are not well-understood.
The invasion potential induced by Id2 was only partially associated with the down-regulation of the metastasis suppressor E-cadherin, suggesting that multiple molecules associated with tumor metastasis may be implicated in this process.
Breast cancer metastasis suppressor 1 (Bregulatesulatexpressioniof of multiple genes linked to metastasis, including osteopontin (OPN), urokinase-type plasminogen activator (uPA), epidermal growth factor receptor (EGFR), fascin, and connexins [ 108].
The SET oncoprotein participates in cancer progression by affecting multiple cellular processes, inhibiting the tumor suppressor protein phosphatase 2A (PP2and and inhibiting the metastasis suppressor nm23-H1.
Breast cancer metastasis suppressor 1 (BRMS1) is a predominantly nuclear protein that differentially regulates expression of multiple genes leading to suppression of metastasis without blocking orthotropic growth (Vaidya and Welch, 2007).This gene is significantly downregulated in some breast tumours, especially in metastatic disease, by epigenetic silencing (Metge et al, 2008).
Breast-cancer metastasis suppressor 1 (BRMS1) gene encodes for a predominantly nuclear protein that differentially regulates the expression of multiple genes, leading to suppression of metastasis without blocking orthotropic tumour growth.
