The Different Gene Expression Profile in the Eutopic and Ectopic Endometrium Sheds New Light on the Endometrial Seed in Endometriosis.

The changes in endometrial cells, both in the eutopic endometrium of patients with and without endometriosis and in lesions at ectopic sites, are frequently described and often compared to tumorigenesis. In tumorigenesis, the concept of "seed and soil" is well established. The seed refers to tumor cells with metastatic potential, and the soil is any organ or tissue that provides a suitable environment for the seed to grow. In this systematic review (PRISMA-S), we specifically compared the development of endometriosis with the "seed and soil" hypothesis. To determine changes in the endometrial seed, we re-analyzed the mRNA expression data of the eutopic and ectopic endometrium, paying special attention to the epithelial-mesenchymal transition (EMT). We found that the similarity between eutopic endometrium without and with endometriosis is extremely high (~99.1%). In contrast, the eutopic endometrium of patients with endometriosis has a similarity of only 95.3% with the ectopic endometrium. An analysis of EMT-associated genes revealed only minor differences in the mRNA expression levels of claudin family members without the loss of other cell-cell junctions that are critical for the epithelial phenotype. The array data suggest that the changes in the eutopic endometrium (=seed) are quite subtle at the beginning of the disease and that most of the differences occur after implantation into ectopic locations (=soil).

The Basic Requirement of Tight Junction Proteins in Blood-Brain Barrier Function and Their Role in Pathologies.

This review addresses the role of tight junction proteins at the blood-brain barrier (BBB). Their expression is described, and their role in physiological and pathological processes at the BBB is discussed. Based on this, new approaches are depicted for paracellular drug delivery and diagnostics in the treatment of cerebral diseases. Recent data provide convincing evidence that, in addition to its impairment in the course of diseases, the BBB could be involved in the aetiology of CNS disorders. Further progress will be expected based on new insights in tight junction protein structure and in their involvement in signalling pathways.

Expression and Localization Profiles of Tight Junction Proteins in Immune Cells Depend on Their Activation Status.

The ability of the immune system to combat pathogens relies on processes like antigen sampling by dendritic cells and macrophages migrating through endo- and epithelia or penetrating them with their dendrites. In addition, other immune cell subtypes also migrate through the epithelium after activation. For paracellular migration, interactions with tight junctions (TJs) are necessary, and previous studies reported TJ protein expression in several immune cells. Our investigation aimed to characterize, in more detail, the expression profiles of TJ proteins in different immune cells in both naïve and activated states. The mRNA expression analysis revealed distinct expression patterns for TJ proteins, with notable changes, mainly increases, upon activation. At the protein level, LSR appeared predominant, being constitutively present in naïve cell membranes, suggesting roles as a crucial interaction partner. Binding experiments suggested the presence of claudins in the membrane only after stimulation, and claudin-8 translocation to the membrane occurred after stimulation. Our findings suggest a dynamic TJ protein expression in immune cells, implicating diverse functions in response to stimulation, like interaction with TJ proteins or regulatory roles. While further analysis is needed to elucidate the precise roles of TJ proteins, our findings indicate important non-canonical functions of TJ proteins in immune response.

Deciphering the complex interplay of obesity, epithelial barrier dysfunction, and tight junction remodeling: Unraveling potential therapeutic avenues.

Obesity stands as a formidable global health challenge, predisposing individuals to a plethora of chronic illnesses such as cardiovascular disease, diabetes, and cancer. A confluence of genetic polymorphisms, suboptimal dietary choices, and sedentary lifestyles significantly contribute to the elevated incidence of obesity. This multifaceted health issue profoundly disrupts homeostatic equilibrium at both organismal and cellular levels, with marked alterations in gut permeability as a salient consequence. The intricate mechanisms underlying these alterations have yet to be fully elucidated. Still, evidence suggests that heightened inflammatory cytokine levels and the remodeling of tight junction (TJ) proteins, particularly claudins, play a pivotal role in the manifestation of epithelial barrier dysfunction in obesity. Strategic targeting of proteins implicated in these pathways and metabolites such as short-chain fatty acids presents a promising intervention for restoring barrier functionality among individuals with obesity. Nonetheless, recognizing the heterogeneity among affected individuals is paramount; personalized medical interventions or dietary regimens tailored to specific genetic backgrounds and allergy profiles may prove indispensable. This comprehensive review delves into the nexus of obesity, tight junction remodeling, and barrier dysfunction, offering a critical appraisal of potential therapeutic interventions.

Molecular alterations in claudin 18 suppressed and non-suppressed gastric adenocarcinomas to guide targeted therapies.

BACKGROUND: Gastric adenocarcinoma represents an aggressive type of cancer and an important cause of cancer mortality. Progress in gastric cancer therapeutics has resulted from a better understanding of the molecular pathogenesis of the disease and introduction of targeted therapies, but most gastric cancer patients still rely on non-targeted chemotherapy as the mainstay of treatment for advanced disease. METHODS: An analysis of publicly available series from The Cancer Genome Atlas (TCGA) gastric cancer cohort was undertaken to delineate the clinical and genomic landscape of gastric cancers with suppressed expression of claudin 18 compared with cancers with non-suppressed claudin 18. Claudin 18 suppressed cancers were defined as having an mRNA expression z-score relative to normal samples (log RNA Seq V2) of less than -1. Claudin 18 non-suppressed cancers were defined as having an mRNA expression z-score relative to normal samples (log RNA Seq V2) above 0.5. RESULTS: Gastric cancers with claudin 18 mRNA suppression represented 7.7% of the gastric adenocarcinomas of TCGA cohort, while non-suppressed cancers represented 46.6% of the cases. The two groups did not differ in clinical and genomic characteristics, such as mean age, histology, grade, and stage. The mutation landscape of claudin 18 suppressed cases included high mutation rates of TP53, of genes of the WNT/ß-catenin pathway and of ubiquitin ligase FBXW7. Moreover, a subset of both claudin 18 suppressed and non-suppressed cancers displayed mutations in Mismatch Repair (MMR) associated genes or a high tumor mutation burden (TMB). At the mRNA expression level, claudin 18 suppressed gastric cancers showed up-regulation of EMT core transcription factor Snail 2 and down-regulation of genes of HLA cluster. The survival of gastric cancer patients with claudin 18 mRNA suppression was not significantly different compared with patients with non-suppressed claudin 18. CONCLUSION: Sub-sets of gastric cancers with claudin 18 mRNA suppression displayed characteristics of potential therapeutic interest, such as mutations in WNT and PI3K pathways and MMR defects. These may guide the development of alternative targeted therapies, in this sub-set of gastric cancers which are not candidates for claudin 18 targeting therapies.

Exploring Potential Biomarkers in Oesophageal Cancer: A Comprehensive Analysis.

Oesophageal cancer (OC) is the sixth leading cause of cancer-related death worldwide. OC is highly aggressive, primarily due to its late stage of diagnosis and poor prognosis for patients' survival. Therefore, the establishment of new biomarkers that will be measured with non-invasive techniques at low cost is a critical issue in improving the diagnosis of OC. In this review, we summarize several original studies concerning the potential significance of selected chemokines and their receptors, including inflammatory proteins such as interleukin-6 (IL-6) and C-reactive protein (CRP), hematopoietic growth factors (HGFs), claudins (CLDNs), matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), adamalysines (ADAMs), as well as DNA- and RNA-based biomarkers, in OC. The presented results indicate the significant correlation between the CXCL12, CXCR4, CXCL8/CXCR2, M-CSF, MMP-2, MMP-9 ADAM17, ADAMTS-6, and CLDN7 levels and tumor stage, as well as the clinicopathological parameters of OC, such as the presence of lymph node and/or distant metastases. CXCL12, CXCL8/CXCR2, IL-6, TIMP-2, ADAM9, and ADAMTS-6 were prognostic factors for the overall survival of OC patients. Furthermore, IL-6, CXCR4, CXCL8, and MMP-9 indicate higher diagnostic utility based on the area under the ROC curve (AUC) than well-established OC tumor markers, whereas CLDN18.2 can be used in novel targeted therapies for OC patients.

Cinnamic Acid and Caffeic Acid Effects on Gastric Tight Junction Proteins Analyzed in Xenopus laevis Oocytes.

Analysis of secondary plant compounds for the development of novel therapies is a common focus of experimental biomedicine. Currently, multiple health-supporting properties of plant-derived molecules are known but still information on many mechanisms is scarce. Cinnamic acid and caffeic acid are two of the most abundant polyphenols in human dietary fruits and vegetables. In this study, we investigated cinnamic acid and caffeic acid effects on the gastric barrier, which is primarily provided by members of the transmembrane tight junction protein family of claudins. The Xenopus laevis oocyte has been established, in recent years, as a heterologous expression system for analysis of transmembrane tight junction protein interactions, by performing paired oocyte experiments to identify an effect on protein-protein interactions, in vitro. In our current study, human gastric claudin-4, -5, and -18.2. were expressed and detected in the oocyte plasma membrane by freeze fracture electron microscopy and immunoblotting. Oocytes were paired and incubated with 100 µM or 200 µM cinnamic acid or caffeic acid, or Ringer's solution, respectively. Caffeic acid showed no effect on the contact area strength of paired oocytes but led to an increased contact area size. In contrast, cinnamic acid-incubated paired oocytes revealed a reduced contact area and a strengthening effect on the contact area was identified. These results may indicate that caffeic acid and cinnamic acid both show an effect on gastric barrier integrity via direct effects on tight junction proteins.

Canonical and Non-Canonical Localization of Tight Junction Proteins during Early Murine Cranial Development.

This study investigates the intricate composition and spatial distribution of tight junction complex proteins during early mouse neurulation. The analyses focused on the cranial neural tube, which gives rise to all head structures. Neurulation brings about significant changes in the neuronal and non-neuronal ectoderm at a cellular and tissue level. During this process, precise coordination of both epithelial integrity and epithelial dynamics is essential for accurate tissue morphogenesis. Tight junctions are pivotal for epithelial integrity, yet their complex composition in this context remains poorly understood. Our examination of various tight junction proteins in the forebrain region of mouse embryos revealed distinct patterns in the neuronal and non-neuronal ectoderm, as well as mesoderm-derived mesenchymal cells. While claudin-4 exhibited exclusive expression in the non-neuronal ectoderm, we demonstrated a neuronal ectoderm specific localization for claudin-12 in the developing cranial neural tube. Claudin-5 was uniquely present in mesenchymal cells. Regarding the subcellular localization, canonical tight junction localization in the apical junctions was predominant for most tight junction complex proteins. ZO-1 (zona occludens protein-1), claudin-1, claudin-4, claudin-12, and occludin were detected at the apical junction. However, claudin-1 and occludin also appeared in basolateral domains. Intriguingly, claudin-3 displayed a non-canonical localization, overlapping with a nuclear lamina marker. These findings highlight the diverse tissue and subcellular distribution of tight junction proteins and emphasize the need for their precise regulation during the dynamic processes of forebrain development. The study can thereby contribute to a better understanding of the role of tight junction complex proteins in forebrain development.

Quercetin Improves Barrier Properties in Porcine Small Intestine but Not in Peyer's Patches.

Peyer's patches (PPs) are part of the gut-associated lymphatic tissue (GALT) and represent the first line of the intestinal immunological defense. They consist of follicles with lymphocytes and an overlying subepithelial dome with dendritic cells and macrophages, and they are covered by the follicle-associated epithelium (FAE). A sealed paracellular pathway in the FAE is crucial for the controlled uptake of luminal antigens. Quercetin is the most abundant plant flavonoid and has a barrier-strengthening effect on tight junctions (TJs), a protein complex that regulates the paracellular pathway. In this study, we aimed to analyze the effect of quercetin on porcine PPs and the surrounding villus epithelium (VE). We incubated both tissue types for 4 h in Ussing chambers, recorded the transepithelial electrical resistance (TEER), and measured the unidirectional tracer flux of [3H]-mannitol. Subsequently, we analyzed the expression, protein amount, and localization of three TJ proteins, claudin 1, claudin 2, and claudin 4. In the PPs, we could not detect an effect of quercetin after 4 h, neither on TEER nor on the [3H]-mannitol flux. In the VE, quercetin led to a higher TEER value, while the [3H]-mannitol flux was unchanged. The pore-forming claudin 2 was decreased while the barrier-forming claudin 4 was increased and the expression was upregulated. Claudin 1 was unchanged and all claudins could be located in the paracellular membrane by immunofluorescence microscopy. Our study shows the barrier-strengthening effect of quercetin in porcine VE by claudin 4 upregulation and a claudin 2 decrease. Moreover, it underlines the different barrier properties of PPs compared to the VE.

Chronic Stress Exposure Alters the Gut Barrier: Sex-Specific Effects on Microbiota and Jejunum Tight Junctions.

Background: Major depressive disorder (MDD) is the leading cause of disability worldwide. Of individuals with MDD, 30% to 50% are unresponsive to common antidepressants, highlighting untapped causal biological mechanisms. Dysfunction in the microbiota-gut-brain axis has been implicated in MDD pathogenesis. Exposure to chronic stress disrupts blood-brain barrier integrity; still, little is known about intestinal barrier function in these conditions, particularly for the small intestine, where absorption of most foods and drugs takes place. Methods: We investigated how chronic social or variable stress, two mouse models of depression, impact the jejunum intestinal barrier in males and females. Mice were subjected to stress paradigms followed by analysis of gene expression profiles of intestinal barrier-related targets, fecal microbial composition, and blood-based markers. Results: Altered microbial populations and changes in gene expression of jejunum tight junctions were observed depending on the type and duration of stress, with sex-specific effects. We used machine learning to characterize in detail morphological tight junction properties, identifying a cluster of ruffled junctions in stressed animals. Junctional ruffling is associated with inflammation, so we evaluated whether lipopolysaccharide injection recapitulates stress-induced changes in the jejunum and observed profound sex differences. Finally, lipopolysaccharide-binding protein, a marker of gut barrier leakiness, was associated with stress vulnerability in mice, and translational value was confirmed on blood samples from women with MDD. Conclusions: Our results provide evidence that chronic stress disrupts intestinal barrier homeostasis in conjunction with the manifestation of depressive-like behaviors in a sex-specific manner in mice and, possibly, in human depression.

Cannabidiol Strengthening of Gastric Tight Junction Complexes Analyzed in an Improved Xenopus Oocyte Assay.

Cannabidiol (CBD), the non-psychoactive compound derived from the cannabis plant, has gained attention in recent years as a remedy against gastrointestinal disorders ranging from nausea and inflammation to abdominal pain. Recent advances demonstrated an effect on inflammatory pathways and barrier proteins. However, information on possible direct effects is scarce and needs to be addressed, as applications are currently increasing in popularity. To accomplish this, we have employed Xenopus laevis oocytes as a heterologous expression system for analysis of the direct effects on stomach-specific claudins and further developed tight junction (TJ) protein interaction assays. Human claudin-4, claudin-5, and claudin-18.2 were expressed in Xenopus oocytes, clustered in pairs to form contact areas, and analyzed in a two-cell model approach, including measurement of the contact area and contact strength. CLDN4/5/18 + CLDN4/5/18 oocyte pairs were incubated with 20 µM CBD or with 40 µM CBD and were compared to cells without CBD treatment (ctrl). For interaction analysis, the contact area was measured after 24 h and 48 h. Whereas CBD did not affect the size of the protein interaction area, Double Orbital Challenge experiments revealed an increased contact strength after 24 h incubation with CBD. In addition, the Xenopus oocyte experiments were accompanied by an analysis of claudin-4, -5, and -18 expression in gastric epithelium by immunoblotting and immunohistochemistry. Claudin-4, -5, and -18 were strongly expressed, indicating a major role for gastric epithelial barrier function. In summary, our study shows direct effects of 40 µM CBD on Xenopus oocytes heterologously expressing a stomach-specific claudin combination, indicating a supportive and beneficial effect of CBD on gastric TJ proteins.

Claudins and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high incidence and dismal prognosis, making it a significant global health burden. To change this, the development of new therapeutic strategies is imminent. The claudin (CLDN) family, as key components of tight junctions (TJs), plays an important role in the initiation and development of cancer. Dysregulated expression of CLDNs leads to loss of intercellular adhesion and aberrant cell signaling, which are closely related to cancer cell invasion, migration, and epithelial-mesenchymal transition (EMT). CLDN1, CLDN3, CLDN4, CLDN5, CLDN6, CLDN7, CLDN9, CLDN10, CLDN11, CLDN14, and CLDN17 are aberrantly expressed in HCC, which drives the progression of the disease. Consequently, they have tremendous potential as prognostic indicators and therapeutic targets. This article summarizes the aberrant expression, molecular mechanisms, and clinical application studies of different subtypes of CLDNs in HCC, with a particular emphasis on CLDN1.

Tight junction and kidney stone disease.

Defects of tight junction (TJ) are involved in many diseases related to epithelial cell functions, including kidney stone disease (KSD), which is a common disease affecting humans for over a thousand years. This review provides brief overviews of KSD and TJ, and summarizes the knowledge on crystal-induced defects of TJ in renal tubular epithelial cells (RTECs) in KSD. Calcium oxalate (CaOx) crystals, particularly COM, disrupt TJ via p38 MAPK and ROS/Akt/p38 MAPK signaling pathways, filamentous actin (F-actin) reorganization and α-tubulin relocalization. Stabilizing p38 MAPK signaling, reactive oxygen species (ROS) production, F-actin and α-tubulin by using SB239063, N-acetyl-L-cysteine (NAC), phalloidin and docetaxel, respectively, successfully prevent the COM-induced TJ disruption and malfunction. Additionally, genetic disorders of renal TJ, including mutations and single nucleotide polymorphisms (SNPs) of CLDN2, CLDN10b, CLDN14, CLDN16 and CLDN19, also affect KSD. Finally, the role of TJ as a potential target for KSD therapeutics and prevention is also discussed.

Expression patterns of claudins in cancer.

Claudins are four-transmembrane proteins, which were found in tight junctions. They maintain cell barriers and regulate cell differentiation and proliferation. They are involved in maintaining cellular polarity and normal functions. Different claudins show different expression patterns. The expression level and localization of claudins are altered in various cancers. They promote or inhibit proliferation, invasion, and migration of cancer cells through multiple signaling pathways. Therefore, claudins may serve as diagnostic markers, novel therapeutic targets, and prognostic risk factors. The important roles of claudins in cancer aroused our great interest. In the present review, we provide a summary of insights into expression patterns of claudins in cancer, which is more comprehensive and provides new ideas for further research.

Tight Junction Claudins and Occludin Are Differentially Regulated and Expressed in Genomically Defined Subsets of Colon Cancer.

Metastatic colon cancer remains incurable despite improvements in survival outcomes. New therapies based on the discovery of colon cancer genomic subsets could improve outcomes. Colon cancers from genomic studies with publicly available data were examined to define the expression and regulation of the major tight junction proteins claudins and occludin in genomic groups. Putative regulations of the promoters of tight junction genes by colon-cancer-deregulated pathways were evaluated in silico. The effect of claudin mRNA expression levels on survival of colon cancer patients was examined. Common mutations in colon-cancer-related genes showed variable prevalence in genomically identified groups. Claudin genes were rarely mutated in colon cancer patients. Genomically identified groups of colon cancer displayed distinct regulation of claudins and occludin at the mRNA level. Claudin gene promoters possessed clustered sites of binding sequences for transcription factors TCF4 and SMADs, consistent with a key regulatory role of the WNT and TGFß pathways in their expression. Although an effect of claudin mRNA expression on survival of colon cancer patients as a whole was not prominent, survival of genomic subsets was significantly influenced by claudin mRNA expression. mRNA expression of the main tight junction genes showed differential regulation in various genomically defined subgroups of colon cancer. These data pinpoint a distinct role of claudins and pathways that regulate them in these subgroups and suggest that subgroups of colon cancer should be considered in future efforts to therapeutically target claudins.

Role of Stress on Driving the Intestinal Paracellular Permeability.

The gut epithelium is a polarized monolayer that exhibits apical and basolateral membrane surfaces. Monolayer cell components are joined side by side via protein complexes known as tight junction proteins (TJPs), expressed at the most apical extreme of the basolateral membrane. The gut epithelium is a physical barrier that determinates intestinal permeability, referred to as the measurement of the transit of molecules from the intestinal lumen to the bloodstream or, conversely, from the blood to the gut lumen. TJPs play a role in the control of intestinal permeability that can be disrupted by stress through signal pathways triggered by the ligation of receptors with stress hormones like glucocorticoids. Preclinical studies conducted under in vitro and/or in vivo conditions have addressed underlying mechanisms that account for the impact of stress on gut permeability. These mechanisms may provide insights for novel therapeutic interventions in diseases in which stress is a risk factor, like irritable bowel syndrome. The focus of this study was to review, in an integrative context, the neuroendocrine effects of stress, with special emphasis on TJPs along with intestinal permeability.

Structural Basis of Clostridium perfringens Enterotoxin Activation and Oligomerization by Trypsin.

Clostridium perfringens enterotoxin (CpE) is a ß-pore forming toxin that disrupts gastrointestinal homeostasis in mammals by binding membrane protein receptors called claudins. Although structures of CpE fragments bound to claudins have been determined, the mechanisms that trigger CpE activation and oligomerization that lead to the formation of cytotoxic ß-pores remain undetermined. Proteolysis of CpE in the gut by trypsin has been shown to play a role in this and subsequent cytotoxicity processes. Here, we report solution structures of full-length and trypsinized CpE using small-angle X-ray scattering (SAXS) and crystal structures of trypsinized CpE and its C-terminal claudin-binding domain (cCpE) using X-ray crystallography. Mass spectrometry and SAXS uncover that removal of the CpE N-terminus by trypsin alters the CpE structure to expose areas that are normally unexposed. Crystal structures of trypsinized CpE and cCpE reveal unique dimer interfaces that could serve as oligomerization sites. Moreover, comparisons of these structures to existing ones predict the functional implications of oligomerization in the contexts of cell receptor binding and ß-pore formation. This study sheds light on trypsin's role in altering CpE structure to activate its function via inducing oligomerization on its path toward cytotoxic ß-pore formation. Its findings can incite new approaches to inhibit CpE-based cytotoxicity with oligomer-disrupting therapeutics.

Finding the junction between claudins and endometrial carcinoma.

Endometrial carcinoma (EC) defines a heterogeneous group of neoplastic diseases originating from the transformation of endometrial cells that constitute the internal lining of the uterus. To date several molecular targets have been analysed to describe the natural course of the disease, claudins being among these. Claudins are the main components of tight junctions (TJs), and their main functions are ascribed to the compartmentalization of tissues and cell-cell communication by means of intracellular ions diffusion: these features are typical of epithelial cells. Their overexpression, mis-localization or loss contribute to the malignancy of EC cells. This review collected all available data regarding the expression, regulation and claudin-related signaling pathways to provide a comprehensive view on the influence of claudin in EC progression. Further, the translational potential of claudin differential expression was explored, indicating that their role in personalized medicine could also contribute to EC therapy besides their employment for diagnosis and prognosis.

Cannabidiol attenuates inflammatory impairment of intestinal cells expanding biomaterial-based therapeutic approaches.

Cannabis-based biomaterials have the potential to deliver anti-inflammatory therapeutics specifically to desired cells, tissues, and organs, enhancing drug delivery and the effectiveness of anti-inflammatory treatment while minimizing toxicity. As a major component of Cannabis, Cannabidiol (CBD) has gained major attention in recent years because of its potential therapeutic properties, e.g., for restoring a disturbed barrier resulting from inflammatory conditions. The aim of this study was to test the hypothesis that CBD has beneficial effects under normal and inflammatory conditions in the established non-transformed intestinal epithelial cell model IPEC-J2. CBD induced a significant increase in transepithelial electrical resistance (TER) values and a decrease in the paracellular permeability of [³H]-D-Mannitol, indicating a strengthening effect on the barrier. Under inflammatory conditions induced by tumor necrosis factor alpha (TNFα), CBD stabilized the TER and mitigated the increase in paracellular permeability. Additionally, CBD prevented the barrier-disrupting effects of TNFα on the distribution and localization of sealing TJ proteins. CBD also affected the expression of TNF receptors. These findings demonstrate the potential of CBD as a component of Cannabis-based biomaterials used in the development of novel therapeutic approaches against inflammatory pathogenesis.

Aberrant Expression of Claudins in Head and Neck Carcinomas and Their Prognostic and Therapeutic Value: A Narrative Review.

Head and neck carcinomas have been associated with poor prognosis. Recent studies have highlighted the role of claudins' expression in tumors throughout the body, and their prognostic and therapeutic role. Understanding the role of claudins and how their expression affects the progression of carcinomas in the head and neck region may allow for advances in the prognosis and management of this type of cancer. Several studies have highlighted the aberrant expression of the proteins in carcinomas in this region. Specifically, the overexpression of claudin-1 and downregulation of claudins-4, -7, and -17 have been linked with poor survival in oral squamous cell carcinoma patients. In laryngeal squamous cell carcinoma, increased levels of claudins-1 and reduced levels of claudins-3, -8, and -11 have been linked with poor outcomes. Targeting these proteins has shown promising outcomes as therapeutic in preclinical studies. However, studies remain extremely limited in nasal and hypopharyngeal carcinomas. In this review, we survey the available literature describing the aberrant expression of various claudins in carcinomas in this region, while highlighting their potential prognostic and therapeutic value. Then, we describe some molecular mechanisms involved in the aberrant expression of claudins and how they can be utilized as therapeutic targets.