Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in melanoma

Timani, Khalid Amine; Győrffy, Balázs; Liu, Ying; Mohammad, Khalid S.; He, Johnny J.

doi:10.1186/s12943-018-0868-z

Cited by 23 publications

(18 citation statements)

References 13 publications

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“…Studies have shown that the expression of IL-8 in melanoma is regulated via NF-κB. When NF-κB is translocated to the nucleus, IL-8 expression increases, leading to the promotion of a more favorable microenvironment for metastasis [80,81]. Our results indicated that both IL-6 and IL-8 expression levels decreased upon diminution of PKC-ι [67].…”

Section: A Schematic Summary Of the Regulation Of The Expression Of Pmentioning

confidence: 54%

Atypical Protein Kinase Cs in Melanoma Progression

Ratnayake¹,

Apostolatos²,

Acevedo‐Duncan³

2019

Cutaneous Melanoma [Working Title]

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Melanoma is one of the fastest growing types of cancer worldwide in terms of incidence. To date, reports show over 92,000 new cases in the United States in 2018. Previously, we introduced protein kinase C-iota (PKC-ι) as an oncogene in melanoma. PKC-ι promotes survival and cancer progression along with PKCzeta(ζ). In addition, we reported that PKC-ι induced metastasis of melanoma cells by increasing Vimentin dynamics. Our previous results showed that PKC-ι inhibition downregulated epithelial-mesenchymal transition (EMT), while inducing apoptosis. In this chapter, we summarized these findings which were based on the in-vitro applications of five specific atypical PKC (aPKC) inhibitors. In addition, the underlying mechanisms of the transcriptional regulation of PRKCI gene expression in melanoma is also discussed. Results demonstrated that c-Jun promotes PRKCI expression along with Interleukin (IL)-6/8. Furthermore, forkhead box protein O1 (FOXO1) acts as a downregulator of PRKCI expression upon stimulation of IL-17E and intercellular adhesion molecule 1 (ICAM-1) in melanoma cells. Overall, the chapter summarizes the importance of PKC-ι/ζ in the progression of melanoma and discusses the cellular signaling pathways that are altered upon inhibitor applications. Finally, we established that aPKCs are effective novel biomarkers for use in the design of novel targeted therapeutics for melanoma.

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Section: A Schematic Summary Of the Regulation Of The Expression Of Pmentioning

confidence: 54%

Atypical Protein Kinase Cs in Melanoma Progression

Ratnayake¹,

Apostolatos²,

Acevedo‐Duncan³

2019

Cutaneous Melanoma [Working Title]

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“…Melanoma cells have been reported to express IL-8 and this influences their oncogenic properties [ 12 , 19 ]. IL-8 follows the evolution of melanoma, progression, and regression under treatment, reflecting the stage of the disease [ 20 – 23 ].…”

Section: Introductionmentioning

confidence: 99%

Antiganglioside Antibodies and Inflammatory Response in Cutaneous Melanoma

Ene

Tampa

Nicolae

et al. 2020

Journal of Immunology Research

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Introduction. Endogenously produced antiganglioside antibodies could affect the evolution of cutaneous melanoma. Epidemiological and experimental evidence suggest “chronic inflammation” to be one of the hallmarks in skin cancers. The aim of the study was to characterize the relation between antiganglioside antibodies and inflammation in cutaneous melanoma focusing on gangliosides GM1, GM2, GM3, GD1a, GD1b, GT1b, GQ1b. Material and Method. We performed an observational study that included 380 subjects subdivided into three groups: patients with metastatic melanoma (170 cases), patients with primary melanoma (160 cases), and healthy subjects (50 subjects). The assessment of antiganglioside antibodies, IgG, and IgM classes, against -GM1, -GM2, -GM3, -GD1a, -GD1b, -GT1b, -GQ1b was performed using immunoblot technique (EUROLine kit). Results. The presence of IgG and IgM antiganglioside antibodies in primary melanoma was (%), as follows: anti-GM1 (5.0 and 13.1), -GM2 (1.8 and 18.1), -GM3 (0.6 and 5.6), -GD1a (0.6 and 15.0), -GD1b (3.7 and 10.7), -GT1b (0.0 and 13.1), -GQ1b (0.0 and 5.0). In metastatic melanoma, the level of antiganglioside antibodies was significantly lower compared with primary melanoma (p<0.05), while in the control group they were absent. Antiganglioside antibodies anti-GM1 and -GD1a were positively correlated, while anti-GM3, -GD1b, and -GT1b were negatively associated with the inflammatory markers, interleukin 8 (IL-8), and C reactive protein (CRP). Conclusions. Tumour ganglioside antigens generate an immune response in patients with primary melanomas. The host’s ability to elaborate an early antiganglioside response could be considered as a defence mechanism, directed toward eliminating a danger signal from the tumour microenvironment. Antiganglioside antibodies associated with inflammation markers could be used as diagnostic, monitoring, and treatment tools in patients with cutaneous melanoma.

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“…Studies have shown that the expression of IL-8 in melanoma is regulated via NF-κB. When NF-κB is translocated to the nucleus, IL-8 expression increases, leading to the promotion of a more favorable microenvironment for metastasis (53,54). The results of this study indicated that both IL-6 and IL-8 expression levels decrease upon transfection with PKC-ι siRNA.…”

Section: Discussionmentioning

confidence: 55%

FOXO1 regulates oncogenic PKC-ι expression in melanoma inversely to c-Jun in an autocrine manner via IL-17E and ICAM-1 activation

Ratnayke

Apostolatos

Breedy

et al. 2018

wasj

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Regardless of abundant efforts to enhance primary prevention and early detection, the number of melanoma cases in the United States has increased steadily over the past 15 years, thus greatly affecting public health and the economy. In previous studies, we demonstrated protein kinase C‑ι (PKC‑ι) to be an oncogene in melanoma, which promotes the activation of nuclear factor (NF)‑κB, thereby supporting survival and progression. In addition, we demonstrated that PKC‑ι induced the metastasis of melanoma cells by activating Vimentin, and PKC‑ι inhibition downregulated epithilial‑mesencymal transition (EMT), while inducing apoptosis. Of note, PKC‑ι specific inhibitors downregulated the expression of both PKC‑ι and phosphorylated PKC‑ι, suggesting that PKC‑ι plays a role in regulating its own expression in melanoma. In this study, we report the underlaying mechanisms of the transcriptional regulation of PKC‑ι (PRKCI gene) expression in melanoma. c‑Jun, interferon‑stimulated gene factor 3 (ISGF3), paired box gene 3 (PAX3), early growth response protein 1 (EGR1) and Forkhead box protein O1 (FOXO1), which bind on or near the promoter sequence of the PRKCI gene, were analyzed for their role in PKC‑ι regulation in SK‑MEL‑2 and MeWo cell lines. We silenced selected transcription factors using siRNA, and the results revealed that the silencing of c‑Jun and FOXO1 significantly altered the expression of PRKCI. The levels of both phosphorylated and total PKC‑ι increased upon FOXO1 silencing and decreased upon c‑Jun silencing, suggesting that c‑Jun acts as an upregulator, while FOXO1 acts as a downregulator of PRKCI expression. We also used a multiplex ELISA to analyze multiple pathways other than NF‑κB that were affected by treatment with PKC‑ι inhibitor. The silencing of NF‑κB p65 and PKC‑ι by siRNA suggested that the regulation of PKC‑ι expression was strongly associated with FOXO1. In addition, we observed a significant decrease in the mRNA levels of both interleukin (IL)‑6 and IL‑8, with a significant increase in the levels of IL‑17E and intercellular adhesion molecule 1 (ICAM‑1) upon the knockdown of expression of PKC‑ι in both cell lines. This suggested that PKC‑ι expression was affected by these cytokines in an autocrine manner. Overall, the findings of this study suggest that PKC‑ι inhibition suppresses its own expression, diminishing oncogenic signaling, while upregulating anti‑tumor signaling, thus rendering it an effective novel biomarker for use in the design of novel targeted therapeutics for melanoma.

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Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in melanoma

Cited by 23 publications

References 13 publications

Atypical Protein Kinase Cs in Melanoma Progression

Atypical Protein Kinase Cs in Melanoma Progression

Antiganglioside Antibodies and Inflammatory Response in Cutaneous Melanoma

FOXO1 regulates oncogenic PKC-ι expression in melanoma inversely to c-Jun in an autocrine manner via IL-17E and ICAM-1 activation

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