VHL promotes immune response against renal cell carcinoma via NF-κB–dependent regulation of VCAM-1

Labrousse-Arias, David; Martínez‐Alonso, Emma; Corral-Escariz, María; Bienes-Martínez, Raquel; Berridy, Jaime; Serrano-Oviedo, Leticia; Conde, Elisa; García‐Bermejo, Maria Laura; Giménez-Bachs, José M.; Salinas-Sánchez, Antonio S.; Sánchez‐Prieto, Ricardo; Yao, Masahiro; Lasa, Marina; Calzada, Marı́a J.

doi:10.1083/jcb.201608024

Cited by 40 publications

(28 citation statements)

References 67 publications

(74 reference statements)

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“…Decreased NF‐κB transcription activity has been associated with reduced VCAM1 adhesion molecule in tumor cells, further impeding the inflammatory status (Hien, Ki, Yang, Oh, & Kang, ). This observation is in line with the described role of NF‐κB in the regulation of VCAM1 expression (Labrousse‐Arias et al, ). Although VCAM1 expression has been proposed to be regulated through the TNF‐α signaling pathway, it seems that NF‐κB signaling acts upstream TNF‐α signaling as despite an increase in the expression of TNFR1, we noticed that VCAM1 was diminished in tumor cells treated with UMB.…”

Section: Discussionsupporting

confidence: 90%

“…MMP2, matrix metalloproteinase 2; VEGF, vascular endothelial growth factor; UMB, umbelliprenin [Color figure can be viewed at wileyonlinelibrary.com] impeding the inflammatory status (Hien, Ki, Yang, Oh, & Kang, 2014). This observation is in line with the described role of NF-κB in the regulation of VCAM1 expression (Labrousse-Arias et al, 2017).…”

supporting

confidence: 69%

“…Downregulation of E-cadherin or any aberration in the function of E-cadherin-related proteins has been strongly associated with the initiation of tumor metastasis in many solid cancers (Beavon, 2000). In addition, we observed a decrease in VCAM1 and NkB expressions, which can also be a contributor in attenuated metastatic behavior (Labrousse-Arias et al, 2017). This is essential as NF-κB signaling has been known to be a potential target in cancer therapy (Sethi, Ahn, Sung, & Aggarwal, 2008).…”

mentioning

confidence: 66%

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Umbelliprenin shows antitumor, antiangiogenesis, antimetastatic, anti‐inflammatory, and immunostimulatory activities in 4T1 tumor‐bearing Balb/c mice

Rashidi

Khalilnezhad

Amani

et al. 2018

Journal Cellular Physiology

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Umbelliprenin (UMB) has shown various pharmacological properties in vitro. We investigated the antineoplastic and immunostimulatory effects of UMB in 4T1 mammary-tumor-bearing mice. Two-hundred microliter of UMB (12.5 mg/ml) was intraperitoneally administrated to healthy and tumor-bearing female Balb/c mice for a period of 18 days. Data was analyzed using GraphPad Prism 5 software for Windows (version 5, La Jolla, CA). UMB caused a significant decrease in tumor size (P < 0.01). Serum interferon gamma (IFNγ) was augmented in both healthy and tumor-bearing animals (P < 0.01), and IL-4 declined in healthy animals (P < 0.01) treated with UMB. Expressions of Ki-67, VEGF, CD31, MMP2, MMP9, VCAM1, and NF-κB were significantly decreased in tumors from UMB-treated animals (P < 0.001), whereas E-Cadherin and TNFR1 expressions were markedly increased (P < 0.001). The rates of liver and lung metastases in UMB-administrated animals were smaller compared to the control. UMB can potently inhibit tumor growth, angiogenesis, metastasis, and inflammation and potentiate an antitumor immune response in vivo. However, further investigations are required to evaluate the UMB mechanisms of action in cancerous cells.

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Section: Discussionsupporting

confidence: 90%

supporting

confidence: 69%

mentioning

confidence: 66%

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Umbelliprenin shows antitumor, antiangiogenesis, antimetastatic, anti‐inflammatory, and immunostimulatory activities in 4T1 tumor‐bearing Balb/c mice

Rashidi

Khalilnezhad

Amani

et al. 2018

Journal Cellular Physiology

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“…However, literature on the effects of the non-canonical NF-κB in RCC is lacking. One study shows that the non-canonical pathway is downregulated in von Hippel-Lindau disease (VHL)-negative RCC cell lines and this results in diminished monocyte cell adhesion [17]. However, in this study, we show that high expression of cytoplasmic NIK and RelB is associated with the downregulation of the local inflammatory infiltrate and poor prognosis, with cytoplasmic NIK being an independent prognostic factor for these patients.…”

Section: Discussioncontrasting

confidence: 46%

The Prognostic Role of the Non-Canonical Nuclear Factor-Kappa B Pathway in Renal Cell Carcinoma Patients

Lua¹,

Qayyum²,

Edwards³

et al. 2018

Urol Int

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Background: In the United Kingdom, 8,000 cases of renal cancer are diagnosed each year, with a 5-year survival rate of 50%. Treatment options are limited; a potential therapeutic target is the non-canonical nuclear factor-kappa B (NF-κB) pathway. This pathway plays a role in multiple oncogenic processes in solid tumors. The aim of this study was to investigate the non-canonical nuclear factor pathway in renal cell carcinoma (RCC). Materials and Methods: NIK, IKKα, and RelB were investigated via immunohistochemistry in a cohort of 192 patients with clear cell renal cancer. Results: High cytoplasmic NIK was associated with poorer cancer-specific survival (p = 0.006) and 10-year survival stratified from 85% (low) to 65% (high, p = 0.005). Similarly, high cytoplasmic RelB was associated with poorer cancer-specific survival (p = 0.041) and 10-year survival stratified from 88% (low) to 73% (high, p = 0.030). When clinicopathological characteristics were assessed, cytoplasmic NIK was associated with survival (p = 0.014), whereas cytoplasmic RelB was associated with increased tumor grade (p = 0.020) and decreased inflammation (p = 0.019). Upon multivariate analysis, it was found that cytoplasmic NIK was independently associated with cancer-specific survival (p = 0.009). Conclusions: The non-canonical NF-κB pathway is associated with poorer cancer-specific survival in RCC patients, making it a viable target for therapeutic intervention. Furthermore, cytoplasmic NIK is a potential prognostic biomarker for this disease.

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“…In this cellular context, Vascular Cell Adhesion Molecule 1 (VCAM-1) expression was found to be regulated by the noncanonical NF-κB pathway. Importantly, VCAM-1 decreased following VHL loss or after hypoxia exposure and PHD inactivation [187]. Recently, the mechanisms by which pVHL might directly impact on the NF-κB pathways have been proposed.…”

Section: Future Prospective In Cancer Therapeutics: Targeting Hif Andmentioning

confidence: 99%

Hypoxia and Inflammation in Cancer, Focus on HIF and NF-кB

D'Ignazio¹,

Batie²,

Rocha³

2017

Preprint

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Cancer is often characterised by the presence of hypoxia and inflammation.Paramount to the mechanisms controlling cellular responses under such stress stimuli, are the transcription factor families of Hypoxia Inducible Factor (HIF) and NuclearFactor of kappa-light-chain-enhancer of activated B cells (NF-κB). Although, a detailed understating of how these transcription factors respond to their cognate stimulus is well established, it is now appreciated that HIF and NF-κB undergo extensive crosstalk, in particular in pathological situations such as cancer. Here, we focus on the current knowledge on how HIF is activated by inflammation and how NF-κB is modulated by hypoxia. We summarise the evidence for the possible mechanism behind this activation and how HIF and NF-κB function impacts cancer, focusing on colorectal, breast and lung cancer. We discuss possible new points of therapeutic intervention aiming to harness the current understanding of the HIF-NF-κB crosstalk.

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VHL promotes immune response against renal cell carcinoma via NF-κB–dependent regulation of VCAM-1

Cited by 40 publications

References 67 publications

Umbelliprenin shows antitumor, antiangiogenesis, antimetastatic, anti‐inflammatory, and immunostimulatory activities in 4T1 tumor‐bearing Balb/c mice

Umbelliprenin shows antitumor, antiangiogenesis, antimetastatic, anti‐inflammatory, and immunostimulatory activities in 4T1 tumor‐bearing Balb/c mice

The Prognostic Role of the Non-Canonical Nuclear Factor-Kappa B Pathway in Renal Cell Carcinoma Patients

Hypoxia and Inflammation in Cancer, Focus on HIF and NF-кB

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