Differential Wnt-β- catenin pathway activation in HPV positive and negative oral epithelium is transmitted during head and neck tumorigenesis: clinical implications

Chakraborty, Balarko; Mukhopadhyay, Debnath; Roychowdhury, Anirban; Basu, Mukta; Alam, Neyaz; Chatterjee, Kabita; Chakrabarti, Jayanta; Panda, Chinmay Kumar

doi:10.1007/s00430-020-00697-9

Cited by 9 publications

(6 citation statements)

References 47 publications

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“…It also displayed a trend towards preferential expression in lymph node metastases. In line with the work of Chakraborty et al, the frequency of alterations for SFRP1 was significantly higher in lymph node positive cases ( p = 0.025), which is in accordance with the reduced expression seen in the tumor group [ 16 ].…”

Section: Discussionsupporting

confidence: 88%

“…HPV infection was strongly relevant with HNSCC, and it was reported to cause approximatively 5% of OSCC cases worldwide [ 21 ]. A previous work showed that the promoter hypermethylation SFRP1 was found in HPV-infected tissues or in cases with tobacco habits, with a downregulation of the Wnt pathway downstream target gene DKK1 and the up-regulation of LRP6 [ 16 ]. Certain limitations were noted in our study.…”

Section: Discussionmentioning

confidence: 99%

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Expression of Tumor Suppressor SFRP1 Predicts Biological Behaviors and Prognosis: A Potential Target for Oral Squamous Cell Carcinoma

et al. 2022

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Background: Genomic instability is implicated in the initiation and progression of oral squamous cell carcinoma (OSCC). Tumor suppressor Secreted Frizzled-Related Protein 1 (SFRP1) may participate in the aberrant evolution of OSCC, the intrinsic molecular mechanisms of which may provide effective therapeutic targets. Methods: A bioinformatics analysis was carried out on a publicly available database using R language to map the prognostic value, immune infiltration and enrichment of SFRP1 expression. Subsequently, in vitro experiments were conducted to unveil the biological function of SFRP1. Results: SFRP1 was found to be ubiquitously lowly expressed in OSCC using a Wilcoxon rank-sum test. Univariate analysis confirmed that those patients characterized by a low SFRP1 expression were significantly associated with advanced T-stage, clinical stage and poor mortality (p < 0.05). Furthermore, SFRP1 displayed a positive performance in tumor immune infiltration, especially in mast cells. Functional annotations indicated that highly expressed SFRP1 was associated with membrane potential and passive transmembrane transporter activity and it was mainly enriched in calcium pathway and neuroactive ligand–receptor interaction. In vitro, the overexpression of SFRP1 inhibited its proliferation, migration, and invasion and resulted in G0+G1 phase arrest within Cal27 cells (p < 0.05). Conclusions: The bioinformation data suggest that SFRP1 expression provides an insight into the risk and prognostic stratification in OSCC. SFRP1 was validated as a potential biomarker with anticarcinogenic behaviors for use in targeted therapy.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Expression of Tumor Suppressor SFRP1 Predicts Biological Behaviors and Prognosis: A Potential Target for Oral Squamous Cell Carcinoma

et al. 2022

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“…Wnt genes are aberrantly expressed in cancers, including HPV‐associated cervical cancer and HNCs 32,33 . FZD, DVL, Wnt4, and Wnt8A genes are upregulated in HPV‐16+ CC compared to normal epithelia 34,35 . The upregulation of WBC genes can occur even in the absence of active HPV infection 36 .…”

Section: Wnt/β‐catenin Signalingmentioning

confidence: 99%

“…Wnt8A genes are upregulated in HPV-16+ CC compared to normal epithelia. 34,35 The upregulation of WBC genes can occur even in the absence of active HPV infection. 36 This, perhaps, indicates that the upregulation of the WBC pathway is a sequential and accumulative effect exerted by E6 and E7.…”

Section: Hpv and Wnt/β-cateninmentioning

confidence: 99%

The effects of HPV oncoproteins on host communication networks: Therapeutic connotations

Skelin,

Luk,

Butorac

et al. 2023

Journal of Medical Virology

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Human papillomavirus (HPV) infections are a leading cause of viral‐induced malignancies worldwide, with a prominent association with cervical and head and neck cancers. The pivotal role of HPV oncoproteins, E5, E6, and E7, in manipulating cellular events, which contribute to viral pathogenesis in various ways, has been extensively documented. This article reviews the influence of HPV oncoproteins on cellular signaling pathways within the host cell, shedding light on the underlying molecular mechanisms. A comprehensive understanding of these molecular alterations is essential for the development of targeted therapies and strategies to combat HPV‐induced premalignancies and prevent their progress to cancer. Furthermore, this review underscores the intricate interplay between HPV oncoproteins and some of the most important cellular signaling pathways: Notch, Wnt/β‐catenin, MAPK, JAK/STAT, and PI3K AKT/mTOR. The treatment efficacies of the currently available inhibitors on these pathways in an HPV‐positive context are also discussed. This review also highlights the importance of continued research to advance our knowledge and enhance therapeutic interventions for HPV‐associated diseases.

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“…This multifunctional protein is an important marker of EMT, and its expression goes hand-in-hand with that of E-cadherin; both adhesion molecules are abnormally expressed when the mesenchymal phenotype takes over. While the cadherin switch allows cancer invasiveness, the Wnt/b-catenin pathway plays a major role in cancer cell proliferation and differentiation [116,134]. While in normal epithelial cells, β-catenin closely cooperates with α-catenin, E-cadherin, and other adhesion molecules towards the stabilization of cell-cell adhesion, in cancer cells this pathway is atypically activated leading to abnormal expression and accumulation of β-catenin in the cytoplasm [135].…”

Section: Wnt/β-catenin Pathwaymentioning

confidence: 99%

Human Papillomavirus and Cellular Pathways: Hits and Targets

2021

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The Human Papillomavirus (HPV) is the causative agent of different kinds of tumors, including cervical cancers, non-melanoma skin cancers, anogenital cancers, and head and neck cancers. Despite the vaccination campaigns implemented over the last decades, we are far from eradicating HPV-driven malignancies. Moreover, the lack of targeted therapies to tackle HPV-related tumors exacerbates this problem. Biomarkers for early detection of the pathology and more tailored therapeutic approaches are needed, and a complete understanding of HPV-driven tumorigenesis is essential to reach this goal. In this review, we overview the molecular pathways implicated in HPV infection and carcinogenesis, emphasizing the potential targets for new therapeutic strategies as well as new biomarkers.

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Differential Wnt-β- catenin pathway activation in HPV positive and negative oral epithelium is transmitted during head and neck tumorigenesis: clinical implications

Cited by 9 publications

References 47 publications

Expression of Tumor Suppressor SFRP1 Predicts Biological Behaviors and Prognosis: A Potential Target for Oral Squamous Cell Carcinoma

Expression of Tumor Suppressor SFRP1 Predicts Biological Behaviors and Prognosis: A Potential Target for Oral Squamous Cell Carcinoma

The effects of HPV oncoproteins on host communication networks: Therapeutic connotations

Human Papillomavirus and Cellular Pathways: Hits and Targets

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