Implications of tyrosine phosphoproteomics in cervical carcinogenesis

Robinson-Bennett, Bernice; DeFord, James H.; Diaz-Arrastia, Concepcion; Levine, Lyuba; Wang, Hui Qui; Hannigan, Edward V.; Papaconstantinou, John

doi:10.1186/1477-3163-7-2

Cited by 13 publications

(14 citation statements)

References 32 publications

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“…Currently, there are only a small number of studies which investigated HPV-infected tumors regarding differences in the proteome [38,39]. To our knowledge, we present here for the first time a proteomic study which investigates (the study) HPV-infected OSCC and we identify/the study identifies differential expressed marker proteins.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of human papillomavirus‐related oral squamous cell carcinoma: Identification of thioredoxin and epidermal‐fatty acid binding protein as upregulated protein markers in microdissected tumor tissue

et al. 2009

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Human papillomavirus (HPV) infection has been identified as an etiologic agent for a subset of oral squamous cell carcinoma (OSCC) with increasing incidence. HPV DNA-positivity may confer better prognosis but the related oncogenic mechanisms are unknown. For the identification of HPV relevant proteins, we analyzed microdissected cells from HPV DNA-positive (n = 17) and HPV DNA-negative (n = 7) OSCC tissue samples. We identified 18 proteins from tumor tissues by peptide fingerprint mapping and SELDI MS that were separated using 2-DE. Among a number of signals that were detected as significantly different in the protein profiling analysis, we identified thioredoxin (TRX) and epidermal-fatty acid binding protein as upregulated in HPV related tumor tissue. This study, investigating for the first time proteomic changes in microdissected HPV infected tumor tissue, provides an indication on the oncogenic potential of viruses.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of human papillomavirus‐related oral squamous cell carcinoma: Identification of thioredoxin and epidermal‐fatty acid binding protein as upregulated protein markers in microdissected tumor tissue

et al. 2009

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“…Although this disease is almost preventable with routine genetic screening and vaccination, more than 80% of cervical cancers with a majority in the advanced stage are currently found in developing countries including China, leading to a high risk of recurrence and poor survival [2,4]. Thus, there is a compelling need to explore novel therapeutic interventions for this disease.…”

Section: Introductionmentioning

confidence: 99%

Activation of AMPK inhibits cervical cancer cell growth through AKT/FOXO3a/FOXM1 signaling cascade

et al. 2013

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BackgroundAlthough advanced-stage cervical cancer can benefit from current treatments, approximately 30% patients may fail after definitive treatment eventually. Therefore, exploring alternative molecular therapeutic approaches is imperatively needed for this disease. We have recently shown that activation of AMP-activated protein kinase (AMPK), a metabolic sensor, hampers cervical cancer cell growth through blocking the Wnt/β-catenin signaling activity. Here, we report that activated AMPK (p-AMPK) also inhibits cervical cancer cell growth by counteracting FOXM1 function.MethodsEffect of the activation of AMPK on FOXM1 expression was examined by hypoxia and glucose deprivation, as well as pharmacological AMPK activators such as A23187, AICAR and metformin. RT Q-PCR and Western blot analysis were employed to investigate the activities of AMPK, FOXM1 and AKT/FOXO3a signaling.ResultsConsistent with our previous findings, the activation of AMPK by either AMPK activators such as AICAR, A23187, metformin, glucose deprivation or hypoxia significantly inhibited the cervical cancer cell growth. Importantly, we found that activated AMPK activity was concomitantly associated with the reduction of both the mRNA and protein levels of FOXM1. Mechanistically, we showed that activated AMPK was able to reduce AKT mediated phosphorylation of p-FOXO3a (Ser253). Interestingly, activated AMPK could not cause any significant changes in FOXM1 in cervical cancer cells in which endogenous FOXO3a levels were knocked down using siRNAs, suggesting that FOXO3a is involved in the suppression of FOXM1.ConclusionTaken together, our results suggest the activated AMPK impedes cervical cancer cell growth through reducing the expression of FOXM1.

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“…Polymorphisms of the Prkdc gene (encoding DNA-PKcs) result in decreased activity and/or expression of DNA-PKcs and have been associated with elevated risk for breast [16, 17], lung [18], gastric [19], colon [20] and cervical [21] cancer. Reduced DNA-PKcs levels have been detected in nuclear cortical extracts from brains of Alzheimer’s disease (AD) patients [22].…”

Section: Introductionmentioning

confidence: 99%

DNA-PKcs deficiency leads to persistence of oxidatively induced clustered DNA lesions in human tumor cells

Peddi

Loftin

Dickey

et al. 2010

Free Radical Biology and Medicine

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DNA-dependent protein kinase (DNA-PK) is a key non-homologous end joining (NHEJ) nuclear serine/threonine protein kinase involved in various DNA metabolic and damage signaling pathways contributing to the maintenance of genomic stability and prevention of cancer. In order to examine the role of DNA-PK in processing of non-DSB clustered DNA damage, we have used three different models of DNA-PK deficiency i.e. chemical inactivation of its kinase activity by novel inhibitors IC86621 and NU7026, knock-down and complete absence of the protein in human breast cancer (MCF-7) and glioblastoma cell lines (MO59-J/K). Compromised DNA-PK repair pathway has lead to accumulation of clustered DNA lesions induced by γ-rays. Tumor cells lacking protein expression or with inhibited kinase activity showed a marked decrease in their ability to process oxidativelyinduced non-DSB clustered DNA lesions measured using a modified version of pulsed field gel electrophoresis or single cell gel electrophoresis (Comet assay). In all cases, DNA-PK inactivation lead to a higher level of lesion persistence even after 24-72 hrs of repair. We suggest a model in which DNA-PK deficiency affects the processing of these clusters by first compromising base excision repair and second by the presence of catalytically inactive DNA-PK inhibiting the efficient processing of these lesions due to the failure of DNA-PK to disassociate from the DNA ends. The information rendered will be important not only for understating cancer etiology in the presence of a NHEJ deficiency but also lead to a better understanding of cancer treatments based on the induction of oxidative stress and inhibition of cluster repair.

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Implications of tyrosine phosphoproteomics in cervical carcinogenesis

Cited by 13 publications

References 32 publications

Proteomic analysis of human papillomavirus‐related oral squamous cell carcinoma: Identification of thioredoxin and epidermal‐fatty acid binding protein as upregulated protein markers in microdissected tumor tissue

Proteomic analysis of human papillomavirus‐related oral squamous cell carcinoma: Identification of thioredoxin and epidermal‐fatty acid binding protein as upregulated protein markers in microdissected tumor tissue

Activation of AMPK inhibits cervical cancer cell growth through AKT/FOXO3a/FOXM1 signaling cascade

DNA-PKcs deficiency leads to persistence of oxidatively induced clustered DNA lesions in human tumor cells

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