Metastasis Suppressors: Basic and Translational Advances

Buchanan, Cecilia; Huvelle, María Amparo Lago; Peters, María Giselle

doi:10.2174/138920111798376914

Cited by 10 publications

(11 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since we have previously shown in a murine model that GPC3 acts as a metastasis suppressor [7][8][9][10], a comprehensive analysis of the molecular mechanism of GPC3 role in the development and progression of human breast cancer is eagerly awaited. We do believe that the progress in GPC3 signaling research will provide new insights to attack targets involved in metastasis, offering unique opportunities for the development of "intelligent" therapeutics, which will lead to novel alternatives to treat breast cancer patients.…”

Section: Time (Month)mentioning

confidence: 99%

“…Regarding mammary gland, we have reported that ectopic GPC3 expression in LM3 (a breast mammary murine GPC3 negative metastatic cell line) was able to inhibit invasion and metastasis [7]. We have determined that GPC3 plays a role in almost all steps of the metastasis cascade by inducing mesenchymal-epithelialtransition (MET), suggesting its role as a metastasis suppressor [8]. Although the GPC3 signaling mechanism is unclear, we found that murine GPC3-reexpressing cells display an inhibition of the canonical Wnt signaling as well as an activation of the non-canonical PCP pathway [9].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expression of Glypican-3 (GPC3) in Malignant and Non-malignant Human Breast Tissues

Castillo¹,

Huvelle²,

Fujita³

et al. 2015

TOCJ

View full text Add to dashboard Cite

Specific reports have linked GPC3 with cancer. Its usefulness as a marker has been proved for hepatocarcinoma, melanoma and ovary carcinoma. However, there are no studies analyzing GPC3 usefulness as a biomarker in mammary tumors. The aim of this work was to analyze GPC3 expression in breast tissues and to determine whether it might be useful as a biomarker in breast cancer patients. Expression level of GPC3 mRNA in Brazilian and Argentine human breast tumor (n=121) and peritumoral "normal" tissue (n=77) samples was analyzed using qRT-PCR. GPC3 protein expression was analyzed from 69 breast cancer and 10 peritumoral samples using IHC. Statistical analyses were done to evaluate the clinical-pathological significance of GPC3 expression. We found that Brazilian and Argentine populations are statistically different regarding GPC3 mRNA expression. In Argentine patients a lower GPC3 mRNA expression was found in tumors as compared to peritumoral tissues. No association was found between GPC3 mRNA and protein expression and the clinical-pathological parameters. The Kaplan-Meier curves suggested that elevated levels of GPC3 mRNA are associated with relapse. Our results indicate differential expression of GPC3 in mammary tumors in comparasion to normal breast tissues. They also suggest the potential role of GPC3 as a biomarker and the importance of deepening the study.

show abstract

Section: Time (Month)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of Glypican-3 (GPC3) in Malignant and Non-malignant Human Breast Tissues

Castillo¹,

Huvelle²,

Fujita³

et al. 2015

TOCJ

View full text Add to dashboard Cite

show abstract

“…Metastasis is defined as the formation of progressively growing secondary tumor foci at sites discontinuous from the primary lesion. To metastasize, carcinoma cells must reactivate a latent embryonic program called epithelial-mesenchymal transition (EMT) [ 3 ]. EMT marks the first step of the “metastasis cascade”, where epithelial cells of the primary tumor acquire mesenchymal-like traits.…”

Section: Introductionmentioning

confidence: 99%

Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells

et al. 2016

View full text Add to dashboard Cite

Breast cancer is the disease with the highest impact on global health, being metastasis the main cause of death. To metastasize, carcinoma cells must reactivate a latent program called epithelial-mesenchymal transition (EMT), through which epithelial cancer cells acquire mesenchymal-like traits.Glypican-3 (GPC3), a proteoglycan involved in the regulation of proliferation and survival, has been associated with cancer. In this study we observed that the expression of GPC3 is opposite to the invasive/metastatic ability of Hs578T, MDA-MB231, ZR-75-1 and MCF-7 human breast cancer cell lines. GPC3 silencing activated growth, cell death resistance, migration, and invasive/metastatic capacity of MCF-7 cancer cells, while GPC3 overexpression inhibited these properties in MDA-MB231 tumor cell line. Moreover, silencing of GPC3 deepened the MCF-7 breast cancer cells mesenchymal characteristics, decreasing the expression of the epithelial marker E-Cadherin. On the other side, GPC3 overexpression induced the mesenchymal-epithelial transition (MET) of MDA-MB231 breast cancer cells, which re-expressed E-Cadherin and reduced the expression of vimentin and N-Cadherin. While GPC3 inhibited the canonical Wnt/β-Catenin pathway in the breast cancer cells, this inhibition did not have effect on E-Cadherin expression. We demonstrated that the transcriptional repressor of E-Cadherin - ZEB1 - is upregulated in GPC3 silenced MCF-7 cells, while it is downregulated when GPC3 was overexpressed in MDA-MB231 cells. We presented experimental evidences showing that GPC3 induces the E-Cadherin re-expression in MDA-MB231 cells through the downregulation of ZEB1.Our data indicate that GPC3 is an important regulator of EMT in breast cancer, and a potential target for procedures against breast cancer metastasis.

show abstract

“…Just as tumor promoters, such as oncogenic Ras or Src, play positive roles in regulating tumorigenesis, a growing body of literature demonstrates a new class of proteins, known as metastasis suppressors, that effectively inhibit metastasis [ 17 , 18 ]. Examples of metastasis suppressors include Kangai1 (KAI1/CD82), E-cadherin, Rho GDP dissociation inhibitor 2 (RhoGDI2), Src-suppressed C kinase substrate (SSeCKS) and N-myc downstream regulated gene 1 (NDRG1) [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

The molecular effect of metastasis suppressors on Src signaling and tumorigenesis: new therapeutic targets

et al. 2015

View full text Add to dashboard Cite

A major problem for cancer patients is the metastasis of cancer cells from the primary tumor. This involves: (1) migration through the basement membrane; (2) dissemination via the circulatory system; and (3) invasion into a secondary site. Metastasis suppressors, by definition, inhibit metastasis at any step of the metastatic cascade. Notably, Src is a non-receptor, cytoplasmic, tyrosine kinase, which becomes aberrantly activated in many cancer-types following stimulation of plasma membrane receptors (e.g., receptor tyrosine kinases and integrins). There is evidence of a prominent role of Src in tumor progression-related events such as the epithelial–mesenchymal transition (EMT) and the development of metastasis. However, the precise molecular interactions of Src with metastasis suppressors remain unclear. Herein, we review known metastasis suppressors and summarize recent advances in understanding the mechanisms of how these proteins inhibit metastasis through modulation of Src. Particular emphasis is bestowed on the potent metastasis suppressor, N-myc downstream regulated gene 1 (NDRG1) and its interactions with the Src signaling cascade. Recent studies demonstrated a novel mechanism through which NDRG1 plays a significant role in regulating cancer cell migration by inhibiting Src activity. Moreover, we discuss the rationale for targeting metastasis suppressor genes as a sound therapeutic modality, and we review several examples from the literature where such strategies show promise. Collectively, this review summarizes the essential interactions of metastasis suppressors with Src and their effects on progression of cancer metastasis. Moreover, interesting unresolved issues regarding these proteins as well as their potential as therapeutic targets are also discussed.

show abstract

Metastasis Suppressors: Basic and Translational Advances

Cited by 10 publications

References 132 publications

Expression of Glypican-3 (GPC3) in Malignant and Non-malignant Human Breast Tissues

Expression of Glypican-3 (GPC3) in Malignant and Non-malignant Human Breast Tissues

Glypican-3 induces a mesenchymal to epithelial transition in human breast cancer cells

The molecular effect of metastasis suppressors on Src signaling and tumorigenesis: new therapeutic targets

Contact Info

Product

Resources

About