Identification and cloning of genes displaying elevated expression as a consequence of metastatic progression in human melanoma cells by rapid subtraction hybridization

Boukerche, Habib; Su, Zao-zhong; Kang, Dong‐Chul; Fisher, Paul B.

doi:10.1016/j.gene.2004.09.002

Cited by 41 publications

(36 citation statements)

References 29 publications

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“…Normal immortal human melanocyte (FM516-SV), M4Beu., a poorly metastatic human melanoma cell line, T1P26 and 7GP highly metastatic variants derived from M4Beu. cells, and MeWo and HO-1 metastatic melanoma cell lines isolated from patients were cultured as described (13,15,24). Rabbit polyclonal antibodies, anti-p50, anti-p65, and InBa were from Santa Cruz Biotechnology (Santa Cruz, CA).…”

Section: Methodsmentioning

confidence: 99%

RETRACTED: mda-9/Syntenin Regulates the Metastatic Phenotype in Human Melanoma Cells by Activating Nuclear Factor-κB

Boukerche¹,

Su²,

Emdad³

et al. 2007

Cancer Research

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mda-9/Syntenin is a scaffolding PDZ domain-containing protein overexpressed in multiple human cancers that functions as a positive regulator of melanoma metastasis. Using a normal immortal human melanocyte cell line and weakly and highly metastatic human melanoma cell lines, we presently show that mda-9/syntenin initiates a signaling cascade that activates nuclear factor-KB (NF-KB) in human melanoma cells. As a consequence of elevated mda-9/syntenin expression, tumor cell growth and motility, fundamental components of tumor cell invasion and metastatic spread of melanoma cells, are enhanced through focal adhesion kinase (FAK)-induced and p38 mitogen-activated protein kinase (MAPK)-induced activation of NF-KB. Inhibiting mda-9/ syntenin, using an adenovirus expressing antisense mda-9/ syntenin, NF-KB, using an adenovirus expressing a mutant superrepressor of IKBA, or FAK, and using a dominantnegative mutant of FAK (FRNK), blocks melanoma cell migration, anchorage-independent growth, and invasion. Downstream signaling changes mediated by mda-9/syntenin, which include activation of FAK, p38 MAPK, and NF-KB, promote induction of membrane-type matrix metalloproteinase-1 that then activates pro-MMP-2-promoting migration and extracellular matrix invasion of melanoma cells. These results highlight the importance of mda-9/syntenin as a key component of melanoma metastasis providing a rational molecular target for potentially intervening in the metastatic process.

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Section: Methodsmentioning

confidence: 99%

RETRACTED: mda-9/Syntenin Regulates the Metastatic Phenotype in Human Melanoma Cells by Activating Nuclear Factor-κB

Boukerche¹,

Su²,

Emdad³

et al. 2007

Cancer Research

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“…We have presently examined the functional role of mda-9/ syntenin in melanoma metastasis using a human melanoma model that closely mimics the early events of metastasis in humans, composed of weakly metastatic versus immunosuppressed newborn rat-selected highly metastatic variants (22)(23)(24). Using recombinant adenoviral vectors expressing either sense or antisense mda-9/syntenin, evidence is now provided indicating that altered mda-9/syntenin expression induces profound phenotypic changes in vitro, which correlates with a dramatic inhibition of the formation of spontaneous lung metastases in an orthotopic rat model in vivo.…”

Section: Introductionmentioning

confidence: 99%

mda-9/Syntenin: A Positive Regulator of Melanoma Metastasis

Boukerche¹,

Su²,

Emdad³

et al. 2005

Cancer Research

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173

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Metastasis is a significant event in cancer progression and continues to pose the greatest challenge for a cancer cure. Defining genes that control metastasis in vivo may provide new targets for intervening in this process with profound therapeutic implications. Melanoma differentiation associated gene-9 (mda-9) was initially identified by subtraction hybridization as a novel gene displaying biphasic expression during terminal differentiation in human melanoma cells. Mda-9, also known as syntenin, is a PDZ-domain protein overexpressed in many types of human cancers, where it is believed to function in tumor progression. However, a functional role of mda-9/ syntenin in tumor growth and metastasis and the signaling pathways involved in mediating these biological activities remain to be defined. Evidence is now provided, using weakly and highly metastatic isogenic melanoma variants, that mda-9/ syntenin regulates metastasis. Expression of mda-9/syntenin correlates with advanced stages of melanoma progression. Regulating mda-9/syntenin expression using a replicationincompetent adenovirus expressing either sense or antisense mda-9/syntenin modifies the transformed phenotype and alters metastatic ability in immortal human melanocytes and metastatic melanoma cells in vitro and in vivo in newborn rats. A direct relationship is observed between mda-9/syntenin expression and increased phosphorylation of focal adhesion kinase, c-Jun-NH 2 -kinase, and p38. This study provides the first direct link between mda-9/syntenin expression and tumor cell dissemination in vivo and indicates that mda-9/syntenin expression activates specific signal transduction pathways, which may regulate melanoma tumor progression. Based on its ability to directly alter metastasis, mda-9/syntenin provides a promising new focus for melanoma cancer research with potential therapeutic applications for metastatic diseases.

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“…Although the transport function of the Na + / K + -ATPase has been investigated extensively in the past, during the last decade multiple lines of evidence have suggested a number of other functions for the sodium pump, revealing NaK as (i) a multifunctional protein with key roles in the formation and maintenance of adhesion complexes, induction of epithelial cell tight junctions and polarity, cell adhesion, motility, and actin dynamics [10][11][12][13][14][15][16][17][18], (ii) a signalling protein [19][20][21][22][23][24][25][26], and (iii) a valuable novel target in anti-cancer therapy because its aberrant expression and activity are implicated in the development and progression of a growing number of cancers [27][28][29][30][31][32][33][34][35][36][37][38]. In addition to the growing number of scientific publications, a number of inventions (recently reviewed in [39]) have also emphasised the potential usefulness of considering NaK expression for future anti-cancer therapy by using it as a diagnostic and prognostic tool, as a biomarker of a therapeutic response in cancer chemotherapy with CS, and as a valuable new target.…”

Section: Resistance Of Cancer Cellsmentioning

confidence: 99%

“…Whether there is isoform-specific mediated sensitivity towards the CS that display anti-cancer effects remains an open question. Currently, most of the published data link the α1 NaK subunit over-expression with cancer progression [27,31,32,[34][35][36][37][38]. Newman et al [45] suggested that rather than an increase or decrease in NaK α subunit expression, the ratio of α3 to α1 should be used as the prognostic indicator for candidate patients to be treated with CS.…”

Section: Mini Reviewsmentioning

confidence: 99%

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2013

Planta Med

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Identification and cloning of genes displaying elevated expression as a consequence of metastatic progression in human melanoma cells by rapid subtraction hybridization

Cited by 41 publications

References 29 publications

RETRACTED: mda-9/Syntenin Regulates the Metastatic Phenotype in Human Melanoma Cells by Activating Nuclear Factor-κB

RETRACTED: mda-9/Syntenin Regulates the Metastatic Phenotype in Human Melanoma Cells by Activating Nuclear Factor-κB

mda-9/Syntenin: A Positive Regulator of Melanoma Metastasis

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