Plasma membrane and nuclear phosphatidylinositol 4,5-bisphosphate signalling in cancer.

The development of metastasis is a leading cause of cancer-related death that involves specific changes in the plasma membrane (PM) and nucleus of cancer cells. Elevated levels of membrane lipids, including sphingomyelin, cholesterol, and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), in the PM, contribute to changes in membrane rigidity, lipid raft formation, and actin polymerisation dynamics, processes that drive cell invasion. This review discusses the relationship between well-studied cytoplasmic phosphoinositides and their lesser-known nuclear counterparts, highlighting their functional role in metastatic progression.

Correction: Köksal et al. Interplay Between HIV and Human Pegivirus (HPgV) Load in Co-Infected Patients: Insights from Prevalence and Genotype Analysis. 2024, , 5.

In the original publication [...

Cytokeratin 17 expression is commonly observed in keratinocytic skin tumours and controls tissue homeostasis impacting human papillomavirus protein expression.

Background: The structured expression of several keratins in the skin is associated with differentiation status of the epidermal layers, whereas other keratins are upregulated only during wound healing, in skin disorders and in cancers. One of these stress keratins, K17, is correlated with poor prognosis in various cancer types and its loss has been shown to decelerate tumour growth. K17 expression can also be detected in cutaneous squamous cell carcinomas, where ultraviolet irradiation and infection with cutaneous human papillomaviruses are important cofactors.

Interplay between HIV and Human Pegivirus (HPgV) Load in Co-Infected Patients: Insights from Prevalence and Genotype Analysis.

Human pegivirus (HPgV) is transmitted through sexual or parenteral exposure and is common among patients receiving blood products. HPgV is associated with lower levels of human immunodeficiency virus (HIV) RNA and better survival among HIV-infected patients. This study aimed to investigate the prevalence of HPgV and determine its subtypes in HIV-infected individuals living in Istanbul, which has the highest rate of HIV infection in Türkiye.

Quantitative super-resolution microscopy reveals the differences in the nanoscale distribution of nuclear phosphatidylinositol 4,5-bisphosphate in human healthy skin and skin warts.

Imaging of human clinical formalin-fixed paraffin-embedded (FFPE) tissue sections provides insights into healthy and diseased states and therefore represents a valuable resource for basic research, as well as for diagnostic and clinical purposes. However, conventional light microscopy does not allow to observe the molecular details of tissue and cell architecture due to the diffraction limit of light. Super-resolution microscopy overcomes this limitation and provides access to the nanoscale details of tissue and cell organization.

Viruses and phospholipids: Friends and foes during infection.

Viruses have evolved complex and dynamic interactions with their host cells to enable viral replication. In recent years, insights have been gained into the increasingly important role of the host cell lipidome in the life cycle of several viruses. In particular, viruses target phospholipid signaling, synthesis, and metabolism to remodel their host cells into an optimal environment for their replication cycle.

MAML1-induced HPV E6 oncoprotein stability is required for cellular proliferation and migration of cervical tumor-derived cells.

While a small proportion of high-risk (HR) alpha (α) human papillomaviruses (HPVs) is associated with numerous human malignancies, of which cervical cancer is the most prevalent, beta (β) HPVs predominantly act as co-factors in skin carcinogenesis. A characteristic feature of both α- and β-E6 oncoproteins is the presence of the LXXLL binding motif, which α-E6s utilize to form a complex with E6AP and which enables β-E6s to interact with MAML1. Here we show that multiple α-E6 oncoproteins bind to MAML1 via the LXXLL binding motif and that this results in increased protein stability.

Poly(I:C) Treatment Prevents Skin Tumor Formation in the Preclinical HPV8 Transgenic Mouse Model.

Actinic keratoses and cutaneous squamous cell carcinomas are associated with infections with human papillomavirus of genus beta (betaHPV) in immunosuppressed patients. To date, targeted therapy against betaHPV-associated skin cancer does not exist because of the large number of betaHPV without defined high-risk types. In this study, we hypothesized that the activation of innate antiviral immunity in the skin, asymptomatically infected with betaHPV, induces an antitumor response by in situ autovaccination and prevents the formation of betaHPV-associated skin cancer.

Human Beta Papillomavirus Type 8 E1 and E2 Proteins Suppress the Activation of the RIG-I-Like Receptor MDA5.

Persistent infections of the skin with the human papillomavirus of genus beta (β-HPV) in immunocompetent individuals are asymptomatic, but in immunosuppressed patients, β-HPV infections exhibit much higher viral loads on the skin and are associated with an increased risk of skin cancer. Unlike with HPV16, a high-risk α-HPV, the impact of β-HPV early genes on the innate immune sensing of viral nucleic acids has not been studied. Here, we used primary skin keratinocytes and U2OS cells expressing HPV8 or distinct HPV8 early genes and well-defined ligands of the nucleic-acid-sensing receptors , , , and to analyze a potential functional interaction.

Subacute thyroiditis after SARS-Cov2 vaccination: A review of the cases being described and personal experience.

The present study evaluates the occurrence of subacute thyroiditis in temporal connection with SARS-Cov2 vaccinations described in the literature last year and confirmed by our clinical routine. Systematic literature search in Medline for studies reporting diagnosis of subacute thyroiditis in temporal connection with vaccinations against Covid 19. The literature search yielded 24 relevant references out of which 22 were "case reports" and two "Letters to the Editor" and encompassed 37 patient cases, in total.

[Role of human papillomavirus (HPV) in the development of skin cancer].

The incidence of nonmelanoma skin cancer, the most common cancer in humans, continues to rise. The development of precancerous actinic keratoses and cutaneous squamous cell carcinoma (cSCC) is associated with infection with human papillomavirus (HPV) of genus beta (betaHPV). Persistent betaHPV infections in immunocompetent individuals are generally very well controlled by the immune system and largely asymptomatic.

HPV8 Reverses the Transcriptional Output in Lrig1 Positive Cells to Drive Skin Tumorigenesis.

K14-HPV8-CER transgenic mice express the complete early genome region of human papillomavirus type 8 (HPV8) and develop skin tumours attributed to the expansion of the Lrig1+ stem cell population. The correlation between HPV8-induced changes in transcriptional output in the stem cell compartment remains poorly understood. To further understand the oncogenic pathways underlying skin tumour formation we examined the gene expression network in skin tumours of K14-HPV8-CER mice and compared the differentially expressed genes (DEG) with those of the Lrig1-EGFP-ires-CreERT2 mice.

Impact of Human Papillomavirus on Wnt/Beta-Catenin Signaling in Morphological Inconspicuous Cervicovaginal Cells.

Introduction: The aim of this study was to identify early changes in the Wnt/beta-catenin signaling pathway in high-risk human papillomavirus (HPV) infected cervicovaginal cells and to correlate these changes with cell proliferation, apoptosis, and autophagic processes.

Methods: We evaluated 91 cervicovaginal smears of women with (n = 41) and without (n = 50) HPV-DNA. Smears were stained against beta-catenin, c-myc, secreted frizzled-related protein 4 (sFRP4), cleaved caspase-3, and the autophagy markers Beclin-1 and light chain 3B.

Genotype Distribution and Prevalence of Human Papillomavirus in Head and Neck Cancer Samples from Istanbul, Turkey.

Human papillomavirus (HPV)-associated tumors account for a significant proportion of head and neck squamous cell carcinomas (HNSCC) in developed countries. In recent years, there has been a rise of HPV infections associated with HNSCC, especially HPV16, which is the most commonly detected type in oral and oropharyngeal cancers. To investigate the frequency of HPV-driven HNSCC among patients living in Turkey, HPV DNA positivity and p16INK4A expression were assessed in primary tumor biopsies (n = 106).

Inactivation of Polyomavirus SV40 as Surrogate for Human Papillomaviruses by Chemical Disinfectants.

Human papillomaviruses (HPV) are non-enveloped DNA viruses infecting cutaneous and mucosal squamous epithelia. Sexually transmitted HPV-types that are carcinogenic to humans such as HPV16 can induce cervical and other anogenital cancers. Virus transmission through fomites such as inadequately disinfected gynecological equipment is a further potential transmission route.

Comprehensive Analysis of VEGFR2 Expression in HPV-Positive and -Negative OPSCC Reveals Differing VEGFR2 Expression Patterns.

VEGF signaling regulated by the vascular endothelial growth factor receptor 2 (VEGFR2) plays a decisive role in tumor angiogenesis, initiation and progression in several tumors including HNSCC. However, the impact of HPV-status on the expression of VEGFR2 in OPSCC has not yet been investigated, although HPV oncoproteins E6 and E7 induce VEGF-expression. In a series of 56 OPSCC with known HPV-status, VEGFR2 expression patterns were analyzed both in blood vessels from tumor-free and tumor-containing regions and within tumor cells by immunohistochemistry using densitometry.

Novel Insights Into Cellular Changes in HPV8-E7 Positive Keratinocytes: A Transcriptomic and Proteomic Analysis.

Human papillomavirus type 8 (HPV8) is associated with the development of non-melanoma skin cancer. In the past we already delved into the mechanisms involved in keratinocyte invasion, showing that the viral E7 oncoprotein is a key player that drives invasion of basal keratinocytes controlled by the extracellular protein fibronectin. To unravel further downstream effects in E7 expressing keratinocytes we now aimed at characterizing gene and protein/phosphoprotein alterations to narrow down on key cellular targets of HPV8-E7.

Frequency of CCR5-Δ32, CCR2-64I and SDF1-3'A alleles in HIV-infected and uninfected patients in Istanbul, Turkey.

Introduction: Co-receptors involved in cell entry of the human immunodeficiency virus (HIV) and mutations in genes encoding their ligands may play a role in the susceptibility to infection and resistance to the progression of the infection. The best studied mutations that can exist in these genes are the CCR5-Δ32, CCR2-64I and SDF1-3'A mutations. The frequency of these mutations vary from continent to continent and even from region to region.

Acquired lymphangioma circumscriptum in high-grade penile intraepithelial neoplasia.

Lymphangioma circumscriptum (LC) is a rare, benign vascular malformation induced by abnormal lymphatic vessels of the skin. LC might be either congenital or acquired, and is predominantly located on the trunk, buttock, axillary region, or thighs. Penile LC is rare.

ATP synthase modulation leads to an increase of spare respiratory capacity in HPV associated cancers.

Mucosal and skin cancers are associated with infections by human papillomaviruses (HPV). The manner how viral oncoproteins hijack the host cell metabolism to meet their own energy demands and how this may contribute to tumorigenesis is poorly understood. We now show that the HPV oncoprotein E7 of HPV8, HPV11 and HPV16 directly interact with the beta subunit of the mitochondrial ATP-synthase (ATP5B), which may therefore represent a conserved feature across different HPV genera.