Overexpression of NF-κB inducing kinase underlies constitutive NF-κB activation in lung cancer cells

Saitoh, Yasunori; Bruyn, Vicente J. Martinez; Uota, Shin; Hasegawa, Atsuhiko; Yamamoto, Naoki; Imoto, Issei; Inazawa, Johji; Shoji, Yasuhiro

doi:10.1016/j.lungcan.2010.03.001

Cited by 29 publications

(30 citation statements)

References 33 publications

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“…The lentiviral vectors capable of expressing an NF-kB-driven firefly luciferase, CS-kB-R2.2 [5], and an EF1a-promoter-driven Renilla luciferase, pCS-EF-1a-Rluc-puro (pCERp) [6] were described previously. pNL4-3luc [7], the pCMV-DR8.2 packaging construct, and a vector capable of expressing the vesicular stomatitis virus G protein (VSV-G), pHCMV-VSV-G, were kind gifts from Dr.…”

Section: Plasmidsmentioning

confidence: 99%

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Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus

Hori

Barnor

Huu

et al. 2015

Biochemical and Biophysical Research Communications

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Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-κB and MAPK signaling pathways because either overexpression of a super-repressor form of IκBα or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by C1. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the C1-induced HIV-1 reactivation. Although C1-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-κB-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainment of HIV-1 expression. These results suggest that procyanidin C1 trimer is a potential compound for reactivation of latent HIV-1 reservoirs.

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Section: Plasmidsmentioning

confidence: 99%

“…The production of VSV-G-pseudotyped NL4-3luc and other lentiviral vectors was described previously ( [5,6,10]). The virus supernatant was harvested at 48 and 60 h post-transfection and was filtered through a 0.45 mm-pore syringe filter.…”

Section: Preparation Of Virus Stocksmentioning

confidence: 99%

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus

Hori

Barnor

Huu

et al. 2015

Biochemical and Biophysical Research Communications

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“…Similar to pancreatic cancer cells, non-small cell lung cancers have elevated NIK expression. Depletion of NIK diminishes constitutive NF-κB activation of both pathways, as well as some survival or metastatic genes such as survivin and MMP-9 [116]. Therefore, depending on cancer types, NIK may regulate one or both NF-κB pathways.…”

Section: The Importance Of Nik In Cancermentioning

confidence: 99%

NF-κB inducing kinase: A key regulator in the immune system and in cancer

Thu

Richmond

2010

Cytokine & Growth Factor Reviews

105

109

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NF-κB inducing kinase (NIK) is a kinase that activates the canonical and non-canonical NF-κB pathways to control transcriptional expression of certain proteins such as cytokines, chemokines and NF-κB signaling molecules. Many advances have been made in understanding the molecular mechanisms by which the stability of NIK is regulated to affect downstream signaling. Genetic mouse models suggest that NIK has an essential role in regulation of the immune system as well as in the bone microenvironment. Increasing evidence links NIK to the tumorigenesis of hematological cancers, such as multiple myeloma, and solid tumors, such as pancreatic carcinoma and melanoma. Understanding the mechanism by which NIK is de-regulated will potentially provide therapeutic options for certain diseases such as autoimmunity and cancer. KeywordsNF-κB inducing kinase (NIK); NF-κB; IKK; canonical pathway; non-canonical pathwayThe nuclear factor-κB (NF-κB) family of transcription factors is comprised of a collection of structurally related proteins that modulate multiple physiological processes, ranging from immune responses to cell death and survival. These transcription factors are ubiquitously expressed and control the expression of a significant number of genes. Multiple kinases and signaling molecules are responsible for the precise regulation of the NF-κB pathway, one of which is NF-κB inducing kinase (NIK). In this review, we will discuss the function and regulation of NIK in relation to its role in the NF-κB pathway, as well as some functions of NIK that are independent of the NF-κB pathway. We will also review the functional significance of NIK in the context of physiological processes such as immune regulation, and in disease models such as autoimmunity and cancer. NIK in the regulation of NF-κB NIK as a kinase of the canonical and non-canonical NF-κB pathwaysThe family of NF-κB in mammals is comprised of five members; p65 (RelA), p105/p50, RelB, p100/p52 and c-Rel. Regulation of NF-κB can be achieved by two distinct pathways.

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“…Depletion of NIK by RNA interference remarkably diminished nuclear NF-κB DNA binding activity and reporter gene expression. These results indicate that NIK plays a key role in constitutive NF-κB acti-vation in NSCLC cells and implicate NIK as a molecular target for lung cancer therapy (27). On the other hand, Sher et al (28) have developed a specific promoter amplification system, called VISA (VP16-GAL4-WPRE integrated systemic amplifier) to enhance the surviving promoter activity (highly expressed in many cancers but not in normal adult tissues) in lung cell lines in vitro and in lung tumor tissue in vivo.…”

Section: Discussionmentioning

confidence: 71%

E phage gene transfection enhances sensitivity of lung and colon cancer cells to chemotherapeutic agents

Prados¹

2010

Int J Oncol

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Abstract. The E gene from ºX174 encodes a membrane protein with a toxic domain that leads to a decrease in the tumour cell growth rate. With the aim of improving the antitumour effect on lung and colon cancer cells of the currently used chemotherapeutic drugs such as gemcitabine, carboplatin and paclitaxel, and 5-fluorouracil (5FU) plus folinic acid (FA) with irinotecan or oxaliplatine, we investigated a new combined therapy using these drugs associated to the transfection of E gene. Our results showed that E gene was able to decrease proliferation rate in A-549 and T-84 cells by inducing apoptotic the mitochondrial pathway. Significantly greater inhibition of proliferation was obtained using drugs in combination with E gene in comparison to single-agent treatments or controls. E gene combined with paclitaxel had the greatest effect on A-549 cells and combined with 5FU/FA/oxaliplatin on T-84 cells. Antitumour mechanisms of the chemotherapeutic drugs were enhanced by E gene, which itself has direct oncolytic effects inducing A-549 and T-84 apoptosis. Our in vitro results indicate that the combined therapy of E gene and cytotoxic drugs may be of potential therapeutic value as a new strategy for patients with advanced lung and colon cancer.

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Overexpression of NF-κB inducing kinase underlies constitutive NF-κB activation in lung cancer cells

Cited by 29 publications

References 33 publications

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus

NF-κB inducing kinase: A key regulator in the immune system and in cancer

E phage gene transfection enhances sensitivity of lung and colon cancer cells to chemotherapeutic agents

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