PHF19 and Akt control the switch between proliferative and invasive states in melanoma

Ghislin, Stéphanie; Deshayes, Frédérique; Middendorp, Sandrine; Boggetto, Nicole; Alcaïde‐Loridan, Catherine

doi:10.4161/cc.20095

Cited by 41 publications

(37 citation statements)

References 44 publications

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“…The theory of dynamic, adaptive phenotype switching is based on the observation that unlike many other solid tumors, melanomas appear to down regulate signaling programs associated with proliferation in order to migrate (1, 2). These proliferative signaling programs are uniquely defined by genes involved in melanocyte differentiation and pigment production, such as MART1 and GP100, which are controlled by the transcription factor MITF.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia Induces Phenotypic Plasticity and Therapy Resistance in Melanoma via the Tyrosine Kinase Receptors ROR1 and ROR2

et al. 2013

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An emerging concept in melanoma biology is that of dynamic, adaptive phenotype switching, where cells switch from a highly proliferative, poorly invasive phenotype to a highly invasive, less proliferative one. This switch may hold significant implications not just for metastasis, but also for therapy resistance. We demonstrate that phenotype switching and subsequent resistance can be guided by changes in expression of receptors involved in the non-canonical Wnt5A signaling pathway, ROR1 and ROR2. ROR1 and ROR2 are inversely expressed in melanomas and negatively regulate each other. Further, hypoxia initiates a shift of ROR1-positive melanomas to a more invasive, ROR2-positive phenotype. Notably, this receptor switch induces a 10-fold decrease in sensitivity to BRAF inhibitors. In melanoma patients treated with the BRAF inhibitor, Vemurafenib, Wnt5A expression correlates with clinical response and therapy resistance. These data highlight the fact that mechanisms that guide metastatic progression may be linked to those that mediate therapy resistance.

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Section: Introductionmentioning

confidence: 99%

Hypoxia Induces Phenotypic Plasticity and Therapy Resistance in Melanoma via the Tyrosine Kinase Receptors ROR1 and ROR2

et al. 2013

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“…PI3K induces PIP3 of second messengers on the cytoplasm membrane after activation, which leads to the activation of Akt. Akt is an important down-stream enzyme that modulates tumor cells in growth, survival, and apoptosis of tumor cells [9]. PI3K increases cell survival rates by Akt, inhibits pro-apoptosis signals, and activates anti-apoptosis genes [10], [11].…”

Section: Introductionmentioning

confidence: 99%

Low Intensity Ultrasound Promotes the Sensitivity of Rat Brain Glioma to Doxorubicin by Down-Regulating the Expressions of P-Glucoprotein and Multidrug Resistance Protein 1 In Vitro and In Vivo

Zhang

et al. 2013

PLoS ONE

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The overall prognosis for malignant glioma is extremely poor, and treatment options are limited in part because of multidrug resistant proteins. Our previous findings suggest low intensity ultrasound (LIUS) can induce apoptosis of glioma cells. Given this finding, we were interested in determining if LIUS could help treat glioma by inhibiting multidrug resistant proteins, and if so, which pathways are involved. In this study, the toxicity sensitivity and multidrug resistance proteins of glioma induced by LIUS were investigated using CCK-8, immunohistochemistry, immunofluorency, and RT-PCR in tissue samples and cultured cells. LIUS inhibited increase of C6 cells in an intensity- and time-dependent manner. The toxicity sensitivity of C6 cells increased significantly after LIUS sonication (intensity of 142.0 mW/cm2) or Doxorubicin (DOX) at different concentration, particularly by the combination of LIUS sonication and DOX. The expressions of P-gp and MRP1 decreased significantly post-sonication at intensity of 142.0 mW/cm2 both in vitro and in vivo. The expressions of p110 delta (PI3K), NF-κB-p65, Akt/PKB, and p-Akt/PKB were downregulated by LIUS sonication and DOX treatment separately or in combination at the same parameters in rat glioma. These results indicate that LIUS could increase the toxicity sensitivity of glioma by down-regulating the expressions of P-gp and MRP1, which might be mediated by the PI3K/Akt/NF-κB pathway.

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“…A previous study confirmed that PHF19 is frequently upregulated in several types of cancer (7). Ghislin et al (9) reported that PHF19 silencing reduced the cell proliferation rate and increased the transendothelial migration capacity of melanoma cell lines. Li et al (10) showed that the expression of PHF19 was increased in glioblastoma multiforme samples and correlated positively with astrocytoma grades.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-195-5p acts as an anti-oncogene by targeting PHF19 in hepatocellular carcinoma

Zhao

et al. 2015

Oncology Reports

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Abstract. Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. PHD finger protein 19 (PHF19) encodes a member of the polycomb group (PcG) of proteins that functions by maintaining the repressive transcriptional states of many developmental regulatory genes. In addition, it has been shown that miR-195 plays an important role in the molecular etiology of HCC; however, the effect and possible mechanism of PHF19 on HCC is unclear, and the association between PHF19 and miR-195 has seldom been addressed. In the present study, we investigated the carcinogenic activity and mechanism of PHF19 on HCC in vivo and in vitro. Our results showed that PHF19 is a potential target of hsa-miR-195-5p based on a bioinformatic analysis and results of a luciferase reporter assay. PHF19 was downregulated after transfection with hsa-miR-195-5p mimics. Moreover, we demonstrated that overexpression of PHF19 promoted hepatoma cell migration, invasion and proliferation in vitro. In contrast, overexpression of hsa-miR-195-5p in hepatoma cells reduced PHF19 expression, leading to suppression of hepatoma cell invasion, migration and proliferation in vitro. In addition, PHF19 markedly promoted the growth of xenograft tumors, while hsa-miR-195-5p markedly suppressed the growth of xenograft tumors in nude mice. These results provide evidence that PHF19 promotes HCC and is regulated by the tumor-suppressor, miR-195-5p.

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PHF19 and Akt control the switch between proliferative and invasive states in melanoma

Cited by 41 publications

References 44 publications

Hypoxia Induces Phenotypic Plasticity and Therapy Resistance in Melanoma via the Tyrosine Kinase Receptors ROR1 and ROR2

Hypoxia Induces Phenotypic Plasticity and Therapy Resistance in Melanoma via the Tyrosine Kinase Receptors ROR1 and ROR2

Low Intensity Ultrasound Promotes the Sensitivity of Rat Brain Glioma to Doxorubicin by Down-Regulating the Expressions of P-Glucoprotein and Multidrug Resistance Protein 1 In Vitro and In Vivo

MicroRNA-195-5p acts as an anti-oncogene by targeting PHF19 in hepatocellular carcinoma

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