The increased expression of Y box‐binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistance

Schittek, Birgit; Psenner, Karin; Sauer, Birgit; Meier, Friedegund; Iftner, Thomas; Garbe, Claus

doi:10.1002/ijc.22512

Cited by 93 publications

(120 citation statements)

References 47 publications

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“…These include PIASy [56], Tip60 [56,57], Y box-binding protein 1 [58,59], p63 [60], and p73 [61]. Both p63 and p73 are rarely mutated in human cancer.…”

Section: Preventing Other Mechanisms From Inactivating P53mentioning

confidence: 99%

Restoring the tumour suppressive function of p53 as a parallel strategy in melanoma therapy

2014

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a b s t r a c tThe tumour suppressor p53 is a master sensor of stress and it controls the expression of hundreds to thousands of genes with diverse biological functions including cell cycle arrest, apoptosis, and senescence. Consequently p53 is the most mutated gene found in human cancer and p53 mutation rate varies from 5% to 95%. Importantly p53 activity is often inactivated in tumours expressing structurally wild type p53. Thus one of the major challenges in cancer research is to restore the tumour suppressive function of p53. Intensive studies in the past decade have demonstrated that in addition to mutation, p53 activities are largely regulated by cellular factors that control the expression level and/or transcriptional activities of p53. MDM2, MDM4, p14ARF and the ASPP family of proteins are among the most studied regulators of p53. With increased understanding of the complexity of p53 regulation, various p53 reactivating approaches are being developed. This review will focus on the recent understanding of p53 inactivation in melanoma and the approaches to reactivate p53 in preclinical studies. Recent success in the therapeutic targeting of the BRAFV600E oncogenic protein was accompanied with subsequent relapse caused by acquired drug resistance.Restoration of the tumour suppressive function of p53 presents a parallel cancer therapeutic opportunity alongside BRAFV600E inhibition. Thus targeted therapy and concurrent reactivation of p53 may be a fertile ground to achieve synergistic killing of the 50% of cancer cells that express structurally wild type p53.

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“…These include PIASy [56], Tip60 [56,57], Y box-binding protein 1 [58,59], p63 [60], and p73 [61]. Both p63 and p73 are rarely mutated in human cancer.…”

Section: Preventing Other Mechanisms From Inactivating P53mentioning

confidence: 99%

Restoring the tumour suppressive function of p53 as a parallel strategy in melanoma therapy

2014

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“…Organotypic skin reconstructs were prepared as previously described (15,16). Melanoma cells were either implemented into the fibroblast containing dermal layer (as spheroids) or seeded together with the keratinocytes as an epidermal layer.…”

Section: Organotypic Skin Culturementioning

confidence: 99%

“…Invasion assays were performed in Boyden chambers coated with a Matrigel basement membrane matrix (BD Biocoat Matrigel invasion chambers, BD Biosciences) as previously described (15). After incubation for 20 hours at 37°C, the invaded cells were fixed and counted after cell staining with H&E or quantified using their lentiviral acquired green fluorescent protein fluorescence.…”

Section: Invasion Assaymentioning

confidence: 99%

Suppression of Casein Kinase 1α in Melanoma Cells Induces a Switch in β-Catenin Signaling to Promote Metastasis

et al. 2010

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Casein kinase 1 α (CK1α) is a multifunctional Ser/Thr kinase that phosphorylates several substrates. Among those is β-catenin, an important player in cell adhesion and Wnt signaling. Phosphorylation of β-catenin by CK1α at Ser45 is the priming reaction for the proteasomal degradation of β-catenin. Interestingly, aside from this role in β-catenin degradation, very little is known about the expression and functional role of CK1α in tumor cells. Here, we show that CK1α expression in different tumor types is either strongly suppressed or completely lost during tumor progression and that CK1α is a key factor determining β-catenin stability and transcriptional activity in tumor cells. CK1α reexpression in metastatic melanoma cells reduces growth in vitro and metastasis formation in vivo, and induces cell cycle arrest and apoptosis, whereas suppression of CK1α in primary melanoma cells induces invasive tumor growth. Inactivation of CK1α promotes tumor progression by regulating a switch in β-catenin-mediated signaling. These results show that melanoma cells developed an efficient new mechanism to activate the β-catenin signaling pathway and define CK1α as a novel tumor suppressor. Cancer Res; 70(17); 6999-7009. ©2010 AACR.

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“…A previous study reported that YBX1, which is involved in malignant transformation of melanocytes, could stimulate proliferation, survival, tumor invasion, and chemoresistance (Schittek et al, 2007). Moreover, downregulation of YBX1 was hypothesized to lead to an increased rate of apoptotic cell death and a reduced rate of proliferation.…”

Section: Discussionmentioning

confidence: 99%

Identifying differential expression genes and single nucleotide variations using RNA-seq in metastatic melanoma

Liu¹,

Zhao²,

Jiao³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Melanoma is a malignant tumor and one of the most frequent metastatic cancers. This study was conducted to identify differential expression genes (DEGs) and single nucleotide variations (SNVs) in metastatic melanoma. We analyzed microarray data of GSE23056 downloaded from the Gene Expression Omnibus, including two normal samples (skinN1 and skinN2) and 2 metastatic melanoma samples (skinT and lymphT). We not only compared DEGs in metastatic melanoma samples with normal samples (lymphT_skinN and skinT_ skinN), but also compared DEGs between two metastatic melanoma types (lymphT_skinT). SNVs were identified by using BurrowsWheeler Aligner and Cufflinks in metastatic melanoma samples using RNA-seq. Sequence Alignment/Map tools and the ANNOVAR software were used to analyze and annotate SNVs. We identified 18 significantly common DEGs in lymphT_skinN and skinT_skinN and one common gene, YBX1, in lymphT_skinN, skinT_skinN, and lymphT_skinT. We identified 49,534, 48,118, 63,812, and 33,096 SNVs in skinN1, skinN2, 8154skinT, and lymphT, respectively. Twenty-nine SNVs were located in exonic regions of two DEGs, HLA-B and TSPAN10. SNVs that exist only in tumors were located in MARVELD1, SLC16A3, and VAV3. The DEGs screened in our study are potential biomarkers for metastatic melanoma therapy.

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The increased expression of Y box‐binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistance

Cited by 93 publications

References 47 publications

Restoring the tumour suppressive function of p53 as a parallel strategy in melanoma therapy

Restoring the tumour suppressive function of p53 as a parallel strategy in melanoma therapy

Suppression of Casein Kinase 1α in Melanoma Cells Induces a Switch in β-Catenin Signaling to Promote Metastasis

Identifying differential expression genes and single nucleotide variations using RNA-seq in metastatic melanoma

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