Table 1.

A list of bona fide metastasis suppressor genes

Pathways targeted	Genes	Tumor type/site	Mech. of action		Type of metastasis
MAPK pathway	NM2337	Breast	1-Phosphorylation of KSR leading to reduced ERK1/2 activation		Reduces both experimental & spontaneous metastases
		Melanoma163–165
			2-LPA signaling54
		Colon166,167
		Oral36,168
	RKIP60	Prostate	Inhibits RAF mediated MAP/ERK kinase phosphorylation		Reduces spontaneous metastases
	MKK466,70,71,72	Prostate, ovarian cancer	MAP2K activates p38 and/or JNK		Reduces spontaneous metastases
	MKK666	Ovarian cancer	Activates MAPK p38		Reduces experimental metastases
	MKK772	Prostate cancer	Activates MAPK JNK		Reduces spontaneous metastases
Adhesion proteins	KAI1169–171	Prostate	Cell adhesion and Integrin signaling		Reduces spontaneous metastases
	CD4489,172,173,174,175	Prostate	Affects cellular adhesion by hyaluronic acid and osteopontin signaling		Reduces spontaneous metastasis
	E-cadherin176,177,178,179	Colon, pancreatic and ovarian cancer	Ca2+ dependent cell adhesion		Reduces spontaneous metastases
Cytoskeletal signaling	Gelsolin106	Melanoma	Actin-regulatory protein helping in actin polymerization		Reduces spontaneous metastasis
	Rho-Rac pathway: RhoGDI2109	Bladder cancer	Rho-Rac signaling		Reduces experimental metastasis
	DLC-1111	Breast cancer	Rho GTPase activating protein which affects cytoskeletal remodeling		Reduces spontaneous metastasis
G-protein-coupled receptors pathway	KISS1114,115	Melanoma	Cytoskeletal reorganization		Reduces both experimental and spontaneous metastases
		Breast116
		Lungs
	Protein kinase A/C pathway: SSeCKS/Gravin/AKAP12120,121,180	Prostate cancer	PKA-mediated activation of Src kinase		Reduces spontaneous metastasis
Apoptotic pathway	Caspase-8123,181,182	Neuroblastoma	Increases integrin-mediated cell death		Reduces spontaneous metastasis
	GAS1124,183	Melanoma	Induces apoptosis through caspases 3 and 9	Reduces spontaneous metastasis
Transcriptional complexes	BRMS1184,185	Melanoma, ovarian cancer	Chromatin remodeling (polyubiquitinated p300, a histone acetyltransferase) and PI3K signaling	Reduces spontaneous metastasis
	MYC141	Breast cancer	Transcriptional silencing of αv and β3 integrin subunits	Reduces spontaneous metastasis
Anti-metastatic miRNAs (Metastamirs)	miR-146a/b147,186	Breast cancer	Reduces NFκB and EGFR pathway	Reduces experimental metastasis
	miR-206	Breast cancer	Target transcription factor S0X4 and extracellular matrix component tenascin C	Reduces experimental metastasis
	miR-335148
Long non-coding RNA (lncRNA)	LncRNA LET153,154	Hepatocellular carcinoma and colon carcinoma	Binds to NF90 and causes its degradation	Reduces experimental metastasis
	NKILA (NFκB-activating lncRNA)155,156	Breast cancer	Negative regulator of NFκB signaling	Reduces experimental metastasis
Metastasis susceptibility genes	Cadm1160	Breast cancer	Sensitizes tumor cells to immune-surveillance mechanisms by CD8+ T cells	Reduces spontaneous metastasis