Constitutive Activation of Nuclear Factor κB Contributes to Cystic Fibrosis Transmembrane Conductance Regulator Expression and Promotes Human Cervical Cancer Progression and Poor Prognosis

Zhao, Weihong; Xue, Peng; Li, Jinke; Zhang, Yi; Hu, Lina

doi:10.1097/igc.0b013e318292da82

Cited by 31 publications

(24 citation statements)

References 32 publications

(33 reference statements)

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“…Since several groups have shown that E1s of various papillomaviruses induce activation of DDR (11-13), we believe that a negative feedback loop between E1 and NF-B might constitute a common mechanism to regulate E1 levels in the basal compartment of the infected tissue. Interestingly, it has been reported that NF-B is upregulated in basal cells of a fraction of CIN1 compared with normal tissues (22). The reported percent NF-B positivity in low-grade cervical lesions has varied from study to study; some authors have indicated that upregulation of NF-B is detected only in cervical cancer while others indicated that it is already present in the basal compartment in 30% of CIN1 lesions (17,19).…”

Section: Activation Of Nf-b By E1 Through Ddrmentioning

confidence: 91%

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Activation of NF-κB by Human Papillomavirus 16 E1 Limits E1-Dependent Viral Replication through Degradation of E1

Nakahara

Tanaka

Ohno

et al. 2015

J Virol

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NF-B is a family of transcription factors that regulate gene expression involved in many processes, such as the inflammatory response and cancer progression. Little is known about associations of NF-B with the human papillomavirus (HPV) life cycle. We have developed a tissue culture system to conditionally induce E1-dependent replication of the human papillomavirus 16 (HPV16) genome in human cervical keratinocytes and found that expression of HPV16 E1, a viral helicase, results in reduction of IB␣ and subsequent activation of NF-B in a manner dependent on helicase activity. Exogenous expression of a degradation-resistant mutant of IB␣, which inhibits the activation of NF-B, enhanced E1-dependent replication of the viral genome. Wortmannin, a broad inhibitor of phosphoinositide 3-kinases (PI3Ks), and, to a lesser extent, VE-822, an ATR kinase inhibitor, but not KU55933, an ATM kinase inhibitor, suppressed the activation of NF-B and augmented E1-dependent replication of the HPV16 genome. Interestingly, the enhancement of E1-dependent replication of the viral genome was associated with increased stability of E1 in the presence of wortmannin as well as the IB␣ mutant. Collectively, we propose that expression of E1 induces NF-B activation at least in part through the ATR-dependent DNA damage response and that NF-B in turn limits E1-dependent replication of HPV16 through degradation of E1, so that E1 and NF-B may constitute a negative feedback loop. IMPORTANCE A major risk factor in human papillomavirus (HPV)-associated cancers is persistent infection with high-risk HPVs. To eradicate viruses from infected tissue, it is important to understand molecular mechanisms underlying the establishment and maintenance of persistent infection. In this study, we obtained evidence that human papillomavirus 16 (HPV16) E1, a viral DNA helicase essential for amplification of the viral genomes, induces NF-B activation and that this limits E1-dependent genome replication of HPV16. These results suggest that NF-B mediates a negative feedback loop to regulate HPV replication and that this feedback loop could be associated with control of the viral copy numbers. We could thus show for the first time that NF-B activity is involved in the establishment and maintenance of persistent HPV infection. Human papillomaviruses (HPVs) are a large family of nonenveloped, small DNA viruses with an approximately 8-kbp double-stranded circular genome that infect stratified squamous epithelium in various anatomical sites such as skin, the anogenital tract, and the oral cavity. Virus infection can cause hyperproliferative lesions, ranging from verrucae to cancer. To date, at least 180 types of HPVs have been cloned from clinical lesions and classified as either cutaneous or mucosal types based on their predilection for different sites of infection. A subset of mucosal HPVs, high-risk HPVs (HR-HPVs), such as HPV16, are strongly associated with anogenital cancers, including nearly 100% of cervical cancers and some proportion of head and neck cancers...

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Section: Activation Of Nf-b By E1 Through Ddrmentioning

confidence: 91%

“…Increased expression of NF-B has been described for HPVassociated lesions such as cervical cancers as well as their precursor lesions and laryngeal papillomas and cancers (17)(18)(19)(20)(21)(22). Several studies have shown that E6 and E7 proteins of HPVs modulate NF-B pathways (23)(24)(25)(26)(27)(28)(29)(30).…”

mentioning

confidence: 99%

Activation of NF-κB by Human Papillomavirus 16 E1 Limits E1-Dependent Viral Replication through Degradation of E1

Nakahara

Tanaka

Ohno

et al. 2015

J Virol

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“…When the CFTR is functional, it is possible ion transportation activities do not account for the main aspect of the tumorigenesis. CFTR has also recently been related to cervical cancer [61][62][63] . A series of studies from Peng et al [61] demonstrated that the expression of CFTR is gradually increased from normal to pre-cancerous cervical tissue and cervical cancer tissues, and it is also positively correlated to histological grades, tumor stage, and metastatic grades.…”

Section: Cftr and Other Cancersmentioning

confidence: 99%

“…A series of studies from Peng et al [61] demonstrated that the expression of CFTR is gradually increased from normal to pre-cancerous cervical tissue and cervical cancer tissues, and it is also positively correlated to histological grades, tumor stage, and metastatic grades. In addition, further investigation by the Peng et al [61] indicated that the upregulated CFTR in pre-cancerous and cervical cancer tissues resulted from aberrantly increased NF-kB p65 translocation [62] . RNA sequencing results obtained from samples co-existing with pre-cancerous lesions and adjacent normal cervical tissue demonstrated that CFTR was also significantly up-regulated in cervical cancer [63] , which is in agreement with the findings from Peng et al [61] and Wu et al [62] .…”

Section: Cftr and Other Cancersmentioning

confidence: 99%

“…In addition, further investigation by the Peng et al [61] indicated that the upregulated CFTR in pre-cancerous and cervical cancer tissues resulted from aberrantly increased NF-kB p65 translocation [62] . RNA sequencing results obtained from samples co-existing with pre-cancerous lesions and adjacent normal cervical tissue demonstrated that CFTR was also significantly up-regulated in cervical cancer [63] , which is in agreement with the findings from Peng et al [61] and Wu et al [62] . These findings are opposite of those from other types of cancers which demonstrated the tumor suppressive roles of CFTR, indicating that the role of CFTR in cancer is organ/system specific.…”

Section: Cftr and Other Cancersmentioning

confidence: 99%

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Emerging role of cystic fibrosis transmembrane conductance regulator - an epithelial chloride channel in gastrointestinal cancers

Hou

Guan

Yang

et al. 2016

WJGO

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Cystic fibrosis transmembrane conductance regulator (CFTR), a glycoprotein with 1480 amino acids, has been well established as a chloride channel mainly expressed in the epithelial cells of various tissues and organs such as lungs, sweat glands, gastrointestinal system, and reproductive organs. Although defective CFTR leads to cystic fibrosis, a common genetic disorder in the Caucasian population, there is accumulating evidence that suggests a novel role of CFTR in various cancers, especially in gastroenterological cancers, such as pancreatic cancer and colon cancer. In this review, we summarize the emerging findings that link CFTR with various cancers, with focus on the association between CFTR defects and gastrointestinal cancers as well as the underlying mechanisms. Further study of CFTR in cancer biology may help pave a new way for the diagnosis and treatment of gastrointestinal cancers.

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Genetic Testing in Cervical Cancer

Sharma,

Singh

2023

Genetic Testing in Reproductive Medicine

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Constitutive Activation of Nuclear Factor κB Contributes to Cystic Fibrosis Transmembrane Conductance Regulator Expression and Promotes Human Cervical Cancer Progression and Poor Prognosis

Cited by 31 publications

References 32 publications

Activation of NF-κB by Human Papillomavirus 16 E1 Limits E1-Dependent Viral Replication through Degradation of E1

Activation of NF-κB by Human Papillomavirus 16 E1 Limits E1-Dependent Viral Replication through Degradation of E1

Emerging role of cystic fibrosis transmembrane conductance regulator - an epithelial chloride channel in gastrointestinal cancers

Genetic Testing in Cervical Cancer

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