C-myc overexpression drives melanoma metastasis by promoting vasculogenic mimicry via c-myc/snail/Bax signaling

Lin, Xian; Sun, Ryan; Zhao, Xiulan; Zhu, Dongwang; Zhao, Xiao‐Fan; Gu, Qing; Dong, Xueyi; Zhang, Danfang; Zhang, Yanhui; Li, Yanlei; Sun, Baocun

doi:10.1007/s00109-016-1452-x

Cited by 84 publications

(57 citation statements)

References 40 publications

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“…A few studies have demonstrated that c-Myc overexpression promotes EMT and facilitates vasculogenic mimicry (VM), 37 wherein vessel-like structures form via aggressive tumor cells. VM has been linked with prolonged tumor angiogenesis, higher metastatic risk and poor outcomes.…”

Section: Discussionmentioning

confidence: 99%

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition

Li¹,

Li²,

Liu³

et al. 2017

IJN

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Angiogenesis is a process by which vessels are formed through preexisting ones, and this plays a key role in the progression of solid tumors. However, tumor vessels are influenced by excessive pro-angiogenic factors, resulting in deformed structures that facilitate the intravasation of tumor cells into the circulation and subsequent metastasis. Moreover, abnormal tumor vessels have low blood perfusion and thereby decreased oxygen infusion into tumors. This results in a hostile microenvironment that promotes epithelial–mesenchymal transition (EMT), a process in which epithelial cells lose their polarity and gain increased motility, which is associated with metastasis and invasion. Here, we demonstrate that gold nanoparticles (AuNPs) facilitate tumor vasculature normalization, increase blood perfusion and alleviate hypoxia in melanoma tumors. Additionally, AuNPs were observed to reverse EMT in tumors, accompanied by the alleviation of lung metastasis. These AuNPs inhibited the migration of B16F10 cells and reversed EMT in B16F10 cells, indicating that AuNPs could directly regulate EMT independent of improvements in hypoxia. Taken together, our data demonstrated that AuNPs could induce tumor vasculature normalization and reverse EMT, resulting in decreased melanoma tumor metastasis.

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Section: Discussionmentioning

confidence: 99%

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition

Li¹,

Li²,

Liu³

et al. 2017

IJN

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“…Increases in the latter prompted us to examine a possible role of c‐Myc as Myc was shown to directly upregulate NOXA in melanoma and pancreatic cancers and also directly regulate BIM . Myc expression is frequently dysregulated and elevated in cancer cells, including melanoma . Myc affects biological functions such as cell division, growth and metabolism and can promote apoptosis if expressed highly .…”

Section: Discussionmentioning

confidence: 99%

“…62,63 Myc expression is frequently dysregulated and elevated in cancer cells, including melanoma. 64,65 Myc affects biological functions such as cell division, growth and metabolism and can promote apoptosis if expressed highly. 63,66 In our study, both BRAFi and HDACi decreased expression of Myc, in agreement with studies on MEK inhibitors in triple negative breast cancer.…”

Section: Discussionmentioning

confidence: 99%

HDAC inhibitors restore BRAF‐inhibitor sensitivity by altering PI3K and survival signalling in a subset of melanoma

Gallagher

Gunatilake

Beaumont

et al. 2017

Intl Journal of Cancer

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Mutations in BRAF activate oncogenic MAPK signalling in almost half of cutaneous melanomas. Inhibitors of BRAF (BRAFi) and its target MEK are widely used to treat melanoma patients with BRAF mutations but unfortunately acquired resistance occurs in the majority of patients. Resistance results from mutations or non-genomic changes that either reactivate MAPK signalling or activate other pathways that provide alternate survival and growth signalling. Here, we show the histone deacetylase inhibitor (HDACi) panobinostat overcomes BRAFi resistance in melanoma, but this is dependent on the resistant cells showing a partial response to BRAFi treatment. Using patient- and in vivo-derived melanoma cell lines with acquired BRAFi resistance, we show that combined treatment with the BRAFi encorafenib and HDACi panobinostat in 2D and 3D culture systems synergistically induced caspase-dependent apoptotic cell death. Key changes induced by HDAC inhibition included decreased PI3K pathway activity associated with a reduction in the protein level of a number of receptor tyrosine kinases, and cell line dependent upregulation of pro-apoptotic BIM or NOXA together with reduced expression of anti-apoptotic proteins. Independent of these changes, panobinostat reduced c-Myc and pre-treatment of cells with siRNA against c-Myc reduced BRAFi/HDACi drug-induced cell death. These results suggest that a combination of HDAC and MAPK inhibitors may play a role in treatment of melanoma where the resistance mechanisms are due to activation of MAPK-independent pathways.

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Section: Discussionmentioning

confidence: 99%

“…Overexpression of the MYC oncogene is known to lead to cellular transformation and dysregulated programmed cell death (Blum, Hao, & McCarthy, 2015;Evan & Littlewood, 1998;Hoffman & Liebermann, 2008;Lin et al, 2017;Meyer & Penn, 2008). Lin et al, (2017) have reported that c-Myc overexpression can increase invasiveness and metastasis of melanomas. Several reports have also shown that amplification of the MYC oncogene is associated with advanced and metastatic melanomas and that it might also be a marker for predicting poor prognosis (Bastian et al, 2002;Grover et al, 1999;Grover, Ross, Wilson, & Sanders, 1997).…”

Section: Discussionmentioning

confidence: 99%

Evolutionary processes of melanomas from giant congenital melanocytic nevi

Lim

Shin

Choi

et al. 2019

Pigment Cell Melanoma Res

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Melanoma can develop in a congenital melanocytic nevus (CMN). In fact, a large CMN is associated with a high risk of developing melanoma. Although melanomas arising from CMNs are thought to have a pathogenesis distinct from conventional melanomas, no studies have been conducted on the evolution or tumor heterogeneity of CMN melanomas. We applied multi‐region whole‐exome sequencing to investigate the clonal nature of driver events and evolutionary processes in CMNs and melanomas arising from CMNs. In two patients, we observed an independent subclonal evolution in cancerized fields of CMNs and chromosome 8q amplification in both melanomas arising from CMNs. The amplification of MYC, located in chromosome 8q, was correlated with the percentage of tumor cells expressing high levels of MYC protein detected in melanoma cells by immunohistochemistry. Our analysis suggests that each CMN cell may evolve sporadically and that amplification of MYC might be a key event for melanoma development in CMNs.

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C-myc overexpression drives melanoma metastasis by promoting vasculogenic mimicry via c-myc/snail/Bax signaling

Cited by 84 publications

References 40 publications

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition

HDAC inhibitors restore BRAF‐inhibitor sensitivity by altering PI3K and survival signalling in a subset of melanoma

Evolutionary processes of melanomas from giant congenital melanocytic nevi

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C-myc overexpression drives melanoma metastasis by promoting vasculogenic mimicry via c-myc/snail/Bax signaling

Cited by 84 publications

References 40 publications

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial&ndash;mesenchymal transition inhibition

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial&ndash;mesenchymal transition inhibition

HDAC inhibitors restore BRAF‐inhibitor sensitivity by altering PI3K and survival signalling in a subset of melanoma

Evolutionary processes of melanomas from giant congenital melanocytic nevi

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Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition

Gold nanoparticles attenuate metastasis by tumor vasculature normalization and epithelial–mesenchymal transition inhibition