Metastasis suppressors genes in cancer

Stafford, Lewis J.; Vaidya, Kedar S.; Welch, Danny R.

doi:10.1016/j.biocel.2007.12.016

Cited by 138 publications

(114 citation statements)

References 152 publications

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“…Nm23-H1 gene is a versatile kinase mapped to 17q.21, a locus (Mathieu et al, 2005). Nm23-H1 homolog is expressed in nucleus and differential expression of Nm23-H1 will enhance metastatic potential (Steeg et al, 1988;Stafford et al, 2008). Nm23-H2 homolog express similarly to that of Nm23-H1 and both protein are extended in function but expressed differentially according to the tissue (Postel et al, 2009).…”

Section: Nm23 Gene Family Isoformsmentioning

confidence: 99%

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Prabhu

Siddikuzzaman²,

Grace³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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The Nm23 gene is a metastatic suppressor identified in a melanoma cell line and expressed in different tumors where their levels of expression are associated with reduced or increased metastatic potential. Nm23 is one of the over 20 metastasis suppressor genes (MSGs) confirmed in vivo. It is highly conserved from yeast to human, implying a critical developmental function. Tumors with alteration of the p53 gene and reduced expression of the Nm23 gene are more prone to metastasis. Nm23-H1 has 3'-5' exonuclease activity. This review focuses on the role of Nm23 in cancer progression and also a potential novel target for cancer therapy.

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Section: Nm23 Gene Family Isoformsmentioning

confidence: 99%

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Prabhu

Siddikuzzaman²,

Grace³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…deaths (Stafford et al, 2008). There are around 20 different metastasis suppressor genes which brings a valuable mechanistic insight for guiding specific therapeutic strategies for cancer including gene transfer, induction of previously suppressed gene expression, exogenous administration of gene product, drug-induced reactivation of metastasis suppressor genes and signalling pathways.…”

Section: Introductionmentioning

confidence: 99%

Kisspeptins (KiSS-1): Essential Players in Suppressing Tumor Metastasis

Prabhu

Sakthivel²,

Guruvayoorappan³

2013

Asian Pacific Journal of Cancer Prevention

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“…This is due to metastatic cells being difficult to detect, highly aggressive, chemoresistant and experimentally challenging to model. 1 At present, there is no agent in clinical use that effectively prevents metastasis and most patients ultimately succumb to metastatic disease.…”

mentioning

confidence: 99%

Withaferin A inhibits breast cancer invasion and metastasis at sub‐cytotoxic doses by inducing vimentin disassembly and serine 56 phosphorylation

Thaiparambil

Bender

Ganesh

et al. 2011

Intl Journal of Cancer

236

208

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Withaferin A (WFA) is purified from the plant Withania somnifera and inhibits the vimentin cytoskeleton. Vimentin overexpression in cancer correlates with metastatic disease, induction of epithelial to mesenchymal transition and reduced patient survival. As vimentin functions in cell motility, we wanted to test the hypothesis that WFA inhibits cancer metastasis by disrupting vimentin function. These data showed that WFA had weak cytotoxic and apoptotic activity at concentrations less than or equal to 500 nM, but retained potent anti-invasive activity at these low doses. Imaging of breast cancer cell lines revealed that WFA induces perinuclear vimentin accumulation followed by rapid vimentin depolymerization. A concomitant induction of vimentin ser56 phosphorylation was observed, which is consistent with vimentin disassembly. Structure activity relationships were established using a set of chemically modified WFA analogs and showed that the predicted vimentin-binding region of WFA is necessary to induce vimentin ser56 phosphorylation and for its anti-invasive activity. Pharmacokinetic studies in mice revealed that WFA reaches peak concentrations up to 2 lM in plasma with a half-life of 1.36 hr following a single 4 mg/kg dose. In a breast cancer metastasis mouse model, WFA showed dose-dependent inhibition of metastatic lung nodules and induced vimentin ser56 phosphorylation, with minimal toxicity to lung tissue. Based upon these studies, we conclude that WFA is a potent breast cancer anti-metastatic agent and the anti-metastatic activity of WFA is, at least in part, mediated through its effects on vimentin and vimentin ser56 phosphorylation.Metastatic disease is the major cause of death in almost all cancer types; however, most treatments are developed to target the primary tumor and not the metastases. This is due to metastatic cells being difficult to detect, highly aggressive, chemoresistant and experimentally challenging to model. 1 At present, there is no agent in clinical use that effectively prevents metastasis and most patients ultimately succumb to metastatic disease.The metastatic process can be broadly categorized into three stages-tumor cell invasion into surrounding tissue, intravasation into blood or lymphatic vessels and extravasation into a new host environment. These events are triggered by genetic and epigenetic alterations that transform stationary epithelial cells into migratory cells, a process termed epithelialmesenchymal transition (EMT). 2,3 Recent data suggests that cancer cells can re-trigger EMT to migrate into surrounding tissue. 3,4 A classical EMT protein is vimentin; numerous reports show that vimentin is overexpressed in invasive human tumors but is nearly undetectable in non-invasive, stationary tumors. 3,[5][6][7] Vimentin is a Type III intermediate filament 8 and its overexpression correlates with metastatic disease, EMT induction, poor prognosis and reduced patient survival. 7,[9][10][11] Similar correlations between vimentin overexpression and invasion are observed in cancer ce...

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Metastasis suppressors genes in cancer

Cited by 138 publications

References 152 publications

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Targeting Tumor Metastasis by Regulating Nm23 Gene Expression

Kisspeptins (KiSS-1): Essential Players in Suppressing Tumor Metastasis

Withaferin A inhibits breast cancer invasion and metastasis at sub‐cytotoxic doses by inducing vimentin disassembly and serine 56 phosphorylation

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