Transcriptional regulation of KiSS-1 gene expression in metastatic melanoma by specificity protein-1 and its coactivator DRIP-130

Mitchell, Donald E.; Stafford, Lewis J.; Li, D.; Bar‐Eli, Menashe; Liu, M.

doi:10.1038/sj.onc.1209963

Cited by 53 publications

(47 citation statements)

References 30 publications

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“…that genes located on chromosome 6 regulate its expression (West et al, 1998;Shirasaki et al, 2001), a fact that was confirmed more recently (Goldberg et al, 2003;Mitchell et al, 2007).…”

mentioning

confidence: 54%

KiSS1 Metastasis Suppressor Gene Product Induces Suppression of Tyrosine Kinase Receptor Signaling to Akt, Tumor Necrosis Factor Family Ligand Expression, and Apoptosis

Navenot¹,

Fujii²,

Peiper³

2009

Molecular Pharmacology

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The powerful metastasis suppressor function of KiSS1 gene products has been demonstrated in both clinical studies and experimental models, but its mechanism is still incompletely understood. Studies on the antimetastatic function of KiSS1 and GPR54 largely focused on the autocrine inhibition of cell motility, despite experimental evidence of an alternative postmigratory effect. We showed previously that the activation of its cognate receptor GPR54 by kisspeptin-10 suppressed the capacity of the prometastatic chemokine receptor CXCR4 to induce chemotaxis in response to stromal cell derived factor 1 and abolished the activation of Akt by CXCR4. We demonstrate here that activation of GPR54 can also abolish the activation of Akt by the tyrosine kinase receptors for epidermal growth factor and insulin. The signaling of GPR54 was sufficient to trigger apoptosis in epithelial and lymphoid cell lines. Surprisingly, this phenomenon depended largely on the activation of extracellular signal-regulated kinase (ERK) rather than the inhibition of Akt. Activation of GPR54 resulted in the ERK-dependent expression of tumor necrosis factor-␣ and FasL in a lymphoid cell line, the latter being the main trigger of apoptosis. These data provide novel mechanisms relevant to a potential autocrine metastasis suppression effect of KiSS1 on GPR54-positive tumor cells. More importantly, they also establish an experimental basis for a paracrine mode of action by which kisspeptins suppress the metastatic potential of tumor cells lacking expression of the receptor, as observed in several animal models of metastasis. The action on stromal cells significantly broadens the clinical relevance of this metastasis suppressor.

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“…that genes located on chromosome 6 regulate its expression (West et al, 1998;Shirasaki et al, 2001), a fact that was confirmed more recently (Goldberg et al, 2003;Mitchell et al, 2007).…”

mentioning

confidence: 54%

KiSS1 Metastasis Suppressor Gene Product Induces Suppression of Tyrosine Kinase Receptor Signaling to Akt, Tumor Necrosis Factor Family Ligand Expression, and Apoptosis

Navenot¹,

Fujii²,

Peiper³

2009

Molecular Pharmacology

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“…It was then shown that this effect was not solely limited to this cancer type by detection in breast cancer (Lee and Welch, 1997b;Martin et al, 2005;Stark et al, 2005;Kostadima et al, 2007;Marot et al, 2007;Mitchell et al, 2007). Most reports associated loss of KISS1 with increasing cancer progression and metastases, although there are contradictions (Martin et al, 2005;Marot et al, 2007).…”

Section: A Metastasismentioning

confidence: 99%

“…However, mapping showed that this gene was in fact located on chromosome 1q32, not 6 . Further studies have determined the presence of a trans-acting regulatory product on chromosome 6 West et al, 1998;Goldberg et al, 2003;Mitchell et al, 2007).…”

Section: A Metastasismentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin Receptor Nomenclature, Distribution, and Function

Kirby

Maguire²,

Colledge³

et al. 2010

Pharmacological Reviews

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“…EMSA was performed as described (Mitchell et al, 2007). For the luciferase reporter assay, 48 hours after transfection of the plasmids the cells in a 24-well plate were lysed and harvested in Reporter Lysis Buffer (Promega).…”

Section: Emsa and Luciferase Reporter Assaymentioning

confidence: 99%

Regulation of bone formation and remodeling by G-protein-coupled receptor 48

et al. 2009

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G-protein-coupled receptor (GPCR) 48 (Gpr48; Lgr4), a newly discovered member of the glycoprotein hormone receptor subfamily of GPCRs, is an orphan GPCR of unknown function. Using a knockout mouse model, we have characterized the essential roles of Gpr48 in bone formation and remodeling. Deletion of Gpr48 in mice results in a dramatic delay in osteoblast differentiation and mineralization, but not in chondrocyte proliferation and maturation, during embryonic bone formation. Postnatal bone remodeling is also significantly affected in Gpr48 -/-mice, including the kinetic indices of bone formation rate, bone mineral density and osteoid formation, whereas the activity and number of osteoclasts are increased as assessed by tartrate-resistant acid phosphatase staining. Examination of the molecular mechanism of Gpr48 action in bone formation revealed that Gpr48 can activate the cAMP-PKA-CREB signaling pathway to regulate the expression level of Atf4 in osteoblasts. Furthermore, we show that Gpr48 significantly downregulates the expression levels of Atf4 target genes/proteins, such as osteocalcin (Ocn; Bglap2), bone sialoprotein (Bsp; Ibsp) and collagen. Together, our data demonstrate that Gpr48 regulates bone formation and remodeling through the cAMP-PKA-Atf4 signaling pathway.

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Transcriptional regulation of KiSS-1 gene expression in metastatic melanoma by specificity protein-1 and its coactivator DRIP-130

Cited by 53 publications

References 30 publications

KiSS1 Metastasis Suppressor Gene Product Induces Suppression of Tyrosine Kinase Receptor Signaling to Akt, Tumor Necrosis Factor Family Ligand Expression, and Apoptosis

KiSS1 Metastasis Suppressor Gene Product Induces Suppression of Tyrosine Kinase Receptor Signaling to Akt, Tumor Necrosis Factor Family Ligand Expression, and Apoptosis

International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin Receptor Nomenclature, Distribution, and Function

Regulation of bone formation and remodeling by G-protein-coupled receptor 48

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