Nuclear factor erythroid 2‐related factor 2 in human papillomavirus‐related cancers

Cruz-Gregorio, Alfredo; Aranda-Rivera, Ana Karina; Pedraza‐Chaverrí, José

doi:10.1002/rmv.2308

Cited by 7 publications

(6 citation statements)

References 133 publications

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“…Previous studies have shown frequent activating mutations of the KEAP1-NRF2 pathway in HNSC along with increased enrichment of its signatures. Other studies have shown suggested alternative mechanisms for activated NRF2 signaling such as upregulation of the c-MYC pathway or by HPV [ 39 , 40 ]. To date, no report has linked mutations in SWI/SNF subunits, such as ARID1A, to activation of NRF2 signaling in HNSC.…”

Section: Discussionmentioning

confidence: 99%

ARID1A loss is associated with increased NRF2 signaling in human head and neck squamous cell carcinomas

Nguyen,

Schrank,

Major

et al. 2024

PLoS ONE

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Prior to the next generation sequencing and characterization of the tumor genome landscape, mutations in the SWI/SNF chromatin remodeling complex and the KEAP1-NRF2 signaling pathway were underappreciated. While these two classes of mutations appeared to independently contribute to tumor development, recent reports have demonstrated a mechanistic link between these two regulatory mechanisms in specific cancer types and cell models. In this work, we expand upon these data by exploring the relationship between mutations in BAF and PBAF subunits of the SWI/SNF complex and activation of NRF2 signal transduction across many cancer types. ARID1A/B mutations were strongly associated with NRF2 transcriptional activity in head and neck squamous carcinomas (HNSC). Many additional tumor types showed significant association between NRF2 signaling and mutation of specific components of the SWI/SNF complex. Different effects of BAF and PBAF mutations on the polarity of NRF2 signaling were observed. Overall, our results support a context-dependent functional link between SWI/SNF and NRF2 mutations across human cancers and implicate ARID1A inactivation in HPV-negative HNSC in promoting tumor progression and survival through activation of the KEAP1-NRF2 signaling pathway. The tumor-specific effects of these mutations open a new area of study for how mutations in the KEAP1-NRF2 pathway and the SWI/SNF complex contribute to cancer.

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Section: Discussionmentioning

confidence: 99%

ARID1A loss is associated with increased NRF2 signaling in human head and neck squamous cell carcinomas

Nguyen,

Schrank,

Major

et al. 2024

PLoS ONE

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“…Interestingly, one of the kinases involved in this pathway also directly phosphorylates transcription factor NRF2 (the product of Nfe2l2 ) in response to environmental stress 91 and NRF2 was predicted to be activated in MnPV‐induced tumors in both datasets (Figures 3C and 5F). Its activation increases the expression of cytoprotective proteins, 44,93 thereby preventing DNA damage and virus integration into the host genome, while its deactivation could cause genome instability 94 . So far, cutaneous PVs are not known to integrate into the host genome and since NRF2 also inhibits the NLRP3 inflammasome, 95 its activation may be a strategy to maintain viral episomes.…”

Section: Discussionmentioning

confidence: 99%

“…Its activation increases the expression of cytoprotective proteins, 44,93 thereby preventing DNA damage and virus integration into the host genome, while its deactivation could cause genome instability. 94 So far, cutaneous PVs are not known to integrate into the host genome and since NRF2 also inhibits the NLRP3 inflammasome, 95 its activation may be a strategy to maintain viral episomes.…”

Section: Discussionmentioning

confidence: 99%

Spatial tissue proteomics reveals distinct landscapes of heterogeneity in cutaneous papillomavirus‐induced keratinocyte carcinomas

Schäfer

Schneider

Müller

et al. 2023

Journal of Medical Virology

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Infection with certain cutaneous human papillomaviruses (HPV), in conjunction with chronic ultraviolet (UV) exposure, are the major cofactors of non‐melanoma skin cancer (NMSC), the most frequent cancer type worldwide. Cutaneous squamous cell carcinomas (SCCs) as well as tumors in general represent three‐dimensional entities determined by both temporal and spatial constraints. Whole tissue proteomics is a straightforward approach to understand tumorigenesis in better detail, but studies focusing on different progression states toward a dedifferentiated SCC phenotype on a spatial level are rare. Here, we applied an innovative proteomic workflow on formalin‐fixed, paraffin‐embedded (FFPE) epithelial tumors derived from the preclinical animal model Mastomys coucha. This rodent is naturally infected with its genuine cutaneous papillomavirus and closely mimics skin carcinogenesis in the context of cutaneous HPV infections in humans. We deciphered cellular networks by comparing diverse epithelial tissues with respect to their differentiation level and infection status. Our study reveals novel regulatory proteins and pathways associated with virus‐induced tumor initiation and progression of SCCs. This approach provides the basis to better comprehend the multistep process of skin carcinogenesis.

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“…Cervical cancer is the fourth most frequently diagnosed malignant disease among women worldwide, with 604,000 new cases in 2020 [39], mainly caused by human papillomavirus (HPV) infection [40]. The integration of the viral genome with the human host is essential for cancer progress, and oxidative stress plays an important role in viral integration and persistent virus infection [41].…”

Section: Cervical Cancermentioning

confidence: 99%

The Dual Role of NRF2 Transcription Factor in Female Cancer

Bruneska Gondim Martins,

Cristina de Aguiar,

Maria de Araújo Barbosa

et al. 2024

The Role of NRF2 Transcription Factor [Working Title]

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Nuclear factor erythroid 2-related factor 2 (NRF2) is an essential transcription factor that is involved in cellular defense against oxidative stress and is assumed to be an important molecule in the transcription and regulation of cytoprotective genes. NRF2 is not only responsible for protecting healthy cells but plays a role in neoplastic cells once high expression of NRF2 has been observed in cancer cells. However, the increase in NRF2 levels may be correlated with resistance to therapy, making it interesting to understand the duality of the protective action of this molecule in the scenario of the cancer hallmarks, NRF2-regulated target genes involved in redox homeostasis, drug metabolism and excretion, amino acid metabolism, iron metabolism, energetic metabolism, survival, autophagy, proliferation, DNA repair, proteasomal degradation, and mitochondrial physiology. Therefore, NRF2 has emerged as a promising target in cancer treatment, and many efforts have been made to identify therapeutic strategies that inhibit its oncogenic role.

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Nuclear factor erythroid 2‐related factor 2 in human papillomavirus‐related cancers

Cited by 7 publications

References 133 publications

ARID1A loss is associated with increased NRF2 signaling in human head and neck squamous cell carcinomas

ARID1A loss is associated with increased NRF2 signaling in human head and neck squamous cell carcinomas

Spatial tissue proteomics reveals distinct landscapes of heterogeneity in cutaneous papillomavirus‐induced keratinocyte carcinomas

The Dual Role of NRF2 Transcription Factor in Female Cancer

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