Catenin Expression Research Articles

The expression of P120 catenin in pancreatic carcinoma and the relationship between the T755G polymorphism of P120 catenin gene and pancreatic carcinoma

To investigate the expression of P120 catenin in pancreatic carcinoma and to explore the association between P120 catenin gene polymorphism at T755G position and pancreatic carcinoma. The expression of P120 catenin in 52 cases of pancreatic carcinoma and normal pancreatic tissues on the mRNA and protein levels were evaluated by RT-PCR and Western Blot methods respectively. P120 catenin gene polymorphism at T755G position of in 52 patients and 60 healthy controls were examined by PCR-restriction fragment length polymorphism (PCR-RFLP) technique. The mRNA and protein expressions of P120 catenin in pancreatic carcinoma tissues were significantly lower than normal pancreatic tissues (P=0.000, P=0.002). Reduced expression of P120 catenin mRNA was significantly correlated with differentiated (P=0.033), lymph node metastasis (P=0.004), vascular invasion (P=0.022), and pTNM stage (P=0.003). Additionally, there were significant difference of P120 catenin gene polymorphism genotypes and alleles at T755G position between patients and healthy controls (P=0.008, P=0.016). The GG genotype of P120 catenin gene was associated with higher risk of incidence for pancreatic carcinoma compared with the TT genotype (OR=2.765, 95%CI=1.312-3.958). The reduced expressions of both P120 catenin mRNA and protein in pancreatic carcinoma suggest its association with pancreatic carcinoma development. Polymorphism of P120 catenin gene at T755G situation might be a risk factor for pancreatic carcinoma, and it may be used to diagnosis and prevent pancreatic carcinoma early.

This Month in Gastroenterology

This Month in Gastroenterology

Modulation of the Tumor Suppressor Protein α-Catenin by Ischemic Microenvironment

Dysregulation or mislocalization of cell adhesion molecules and their regulators, such as E-cadherin, beta-catenin, and alpha-catenin, usually correlates with loss of polarity, dedifferentiation, invasive tumor growth, and metastasis. A subpopulation of alpha-catenin-negative cells within the DLD-1 colorectal carcinoma cell line causes it to display a heterogeneous morphological makeup, thus providing an excellent model system in which to investigate the role of alpha-catenin in tumorigenesis. We re-established expression of alpha-catenin protein in an alpha-catenin-deficient subpopulation of the DLD-1 cell line and used it to demonstrate that loss of alpha-catenin resulted in increased in vitro tumorigenic characteristics (increased soft agarose colony formation, clonogenic survival after suspension, and survival in suspension). When the cells were used to form tumor xenografts, those lacking alpha-catenin showed faster growth rates because of increased cellular cycling but not increased tumor microvascular recruitment. alpha-Catenin-expressing cells were preferentially located in well perfused areas of xenografts when tumors were formed from mixed alpha-catenin-positive and -negative cells. We therefore evaluated the role of the ischemic tumor microenvironment on alpha-catenin expression and demonstrated that cells lose expression of alpha-catenin after prolonged exposure in vitro to hypoglycemic conditions. Our findings illustrate that the tumor microenvironment is a potent modulator of tumor suppressor expression, which has implications for localized nutrient deficiency and ischemia-induced cancer progression.

8018 CTNNB1 promoter methylation in ovarian carcinomas is associated with loss of beta catenin expression and poor patient survival

Nonalcoholic fatty liver disease (NAFLD) is a condition characterized by the excessive accumulation of triglycerides in hepatocytes. NAFLD is the most frequent chronic liver disease in developed countries, and is often associated with metabolic disorders such as obesity and type 2 diabetes. NAFLD definition encompasses a spectrum of chronic liver abnormalities, ranging from simple steatosis (NAFL), to steatohepatitis (NASH), significant liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD, therefore, represents a global public health issue. Mitochondrial dysfunction occurs in NAFLD, and contributes to the progression to the necro-inflammatory and fibrotic form (NASH). Disrupted mitochondrial function is associated with a decrease in the energy levels and impaired redox balance, and negatively affects cell survival by altering overall metabolism and subcellular trafficking. Such events reduce the tolerance of hepatocytes towards damaging hits, and favour the injurious effects of extra-cellular factors. Here, we discuss the role of mitochondria in NAFLD and focus on potential therapeutic approaches aimed at preserving mitochondrial function.

Expression and Clinical Significance of P120 Catenin mRNA and Protein in Pancreatic Carcinoma

The aim of this work was investigate the association of P120 catenin expression with the clinicopathologic features and prognosis of pancreatic carcinoma. RT-PCR was performed to investigate the expression of P120 catenin mRNA and western blotting were performed to investigate the expression of P120 catenin protein in 52 patients with pancreatic carcinoma. The relationships between P120 catenin expression and clinicopathological characteristics and prognosis were analyzed. The mRNA and protein expression of P120 catenin detected by RT-PCR and western blotting in pancreatic carcinoma was significantly lower than that in normal pancreatic tissues (0.227+/-0.067 vs 0.793+/-0.162, t=9.157, P =0.000; 0.665+/-0.192 vs 0.936+/-0.251, t=3.857, P=0.002). Reduced expression of P120 catenin mRNA and protein was significantly correlated with lymph node metastasis (P =0.004, P =0.006), vascular invasion (P =0.022, P =0.039 ), distant metastasis (P =0.037 , P =0.025), differentiated (P =0.033, P =0.013) and pTNM stage (P =0.003, P =0.022) of tumours. Additionally, reduced expression of P120 catenin mRNA and protein in tumour correlated with a worse prognosis and normal expression with a better survival rate (P=0.022, P=0.007). The reduced expression of both P120 catenin mRNA and protein in pancreatic carcinoma suggest that low expressions relate to pancreatic carcinoma development. P120 catenin may be related to pancreatic carcinoma behaviour and be a potential prognostic molecule.

Adhesion molecules α, β and γ‐catenin as prognostic factors of tumour progression in upper urinary tract urothelial tumours: the role of AKT‐P/GSK‐3β/β‐catenin pathway

OBJECTIVES To evaluate alpha, beta and gamma-catenin expression in upper urinary tract urothelial tumours (UUTC) and determine their value as prognostic factors; to investigate the correlation between the catenin complex and the AKT pathway. PATIENTS AND METHODS We retrospectively analysed 114 consecutive patients treated at our institution from 1990 to 2004; the mean follow-up was 54 months. Tumour samples were available from 70 patients, and included in tissue microarrays for immunohistochemical analysis. The antibodies used were anti-alpha, -beta and gamma-catenin, and antiphospho-AKT. The prognostic value of the expression of these molecules was analysed using tumour progression and cancer-specific survival as end-points. RESULTS Of the 114 patients, 27% developed tumour progression; the cancer-specific and overall survival were 77% and 60.6%, respectively. Abnormal alpha, beta and gamma-catenin expression was found in 44 (63%), 22 (31%) and 28 (41%) patients, respectively; the abnormal catenin expression patterns correlated with each other. Positive cytoplasm phospho-AKT expression was found in 27 (39%) patients. Three of them were found to have cytoplasmic beta-catenin accumulation and none of them nuclear expression. beta-catenin expression was the only one that was an independent marker of tumour progression, with a hazard ratio (95% confidence interval) of 3.1(1.2-8.6), together with grade (7.1, 1.2-55.8) and stage (4.6, 2.1-10). In the cancer-specific survival analysis, again beta-catenin was an independent prognostic factor (3.4, 1-11.5) together with stage (4.6, 2.2-9.8). CONCLUSIONS The loss of the normal membrane beta-catenin expression constitutes an independent factor of tumour progression and cancer-specific survival. Our data suggest that the AKT/GSK3beta/beta-catenin signalling pathway is not activated in the UUTC carcinogenesis.

A DISCREET EPITHELIAL POPULATION DERIVED FROM HUMAN PROSTATE TISSUE DEMONSTRATES STEM/PROGENITOR CELL ACTIVITY

TURP. Representative tissue confirmed histological diagnoses, whilst disaggregated PECs underwent isolation of the DSP, Proximal-SP (PSP) and Non-SP (NSP) and cell cycle analysis using fluorescence-activated cell sorting (FACS) protocols. Populations were immunohistochemically characterised and clonogenicity was assessed in monolayer culture. The DSP, PSP and NSP from 8 normal, 6 BPH and 6 CaP patients were isolated under RNAse-free conditions and RNA was extracted using the Qiagen RNeasy Mini Kit. cDNA was created and amplified using Nalgene small cell number chemistries prior to HG-U133 Plus-2 Affymetrix Microarray chip hybridisation. RESULTS: A DSP, comprising 0.025% of the total PEC population (n=15) was isolated. The DSP was low in CD133 (p=0.002), CK-8 (p=0.005) and p63 (p=0.001), but enriched for -Catenin (p=0.024), p27 (p=0.04) and Notch-1 (p=0.042) expression as compared with the PSP and had a 2.16-fold enhanced clonogenicity (p=0.026). High quality RNA (RNA Integrity Number >6.3) was successfully extracted despite small numbers of quiescent cells (mean RNA 3.61μg, range 0.45-35.1μg). Gene calls were equivalent to those seen in cell line experiments (mean 50.19%). Pearson correlation efficients revealed good inter-population array correlation. CONCLUSIONS: The distal SP is highly enriched for cells with stem characteristics. Microarray analysis of this small population has enabled, for the first time using such low cell numbers, comparison of unexpanded normal, benign and malignant PECs, based on their dye efflux status. This unique data can now be interrogated to identify novel biomarkers, regulatory pathways and genetic changes in the SC compartment of these cells. Information gained therefrom will facilitate further study of the prostate SC.

The Loss of E-cadherin is Associated with the Epigenetic Alteration of CDH1 in Breast Cancer and it is also Associated with an Abnormal β-catenin Expression in Lobular Carcinoma

Background : APC and E-cadherin are the key molecules in the Wnt/-catenin pathway. We attempted to define the epigenetic alteration of APC and CDH1 (the E-cadherin gene) and the expression of Wnt-related molecules in human mammary carcinomas. Methods : Sixtyfour mammary carcinomas, including 52 invasive ductal carcinomas (IDCs) and 12 invasive lobular carcinomas (ILCs), were evaluated using methylation-specific PCR and immunohistochemistry. We performed immunohistochemistry for E-cadherin, -catenin, APC, Wnt1, cyclin D1, ER, PR and C-erb B2. Results : Hypermethylation of APC and CDH1 was observed in 38 (59%) and 28 (44%) cases, respectively. CDH1 hypermethylation in ILCs was increased compared to that in IDCs (p=0.002) and it was associated with the loss of E-cadherin (p=0.02) and -catenin (p=0.042). APC methylation was positively correlated with the ER expression (p=0.021). Abnormal cytoplasmic localization of -catenin was found in 10 cases and any expression was not detected in six cases. In ILCs, the E-cadherin or -catenin expression was markedly decreased compared to that in IDCs (p-catenin expression was related to the loss of E-cadherin in ILC.

Expression of Alpha-catenin/E-cadherin and Clinical Significance of Metastatic Factors in Stage III Advanced Colon Cancer

Purpose: Among the cell adhesion molecules, α -catenin and E-cadherin play an important part in maintaining normal cell structure. The change in expression of cell adhesion molecules affects the invasion and metastasis of a tumor and the prognosis for patients. In this study, we evaluated the relationship between the expression of cell adhesion molecules and the histopathologic characteristics of stage III colon cancer. Methods: The relationship between the immunohistochemical expression of cell adhesion molecules and tumor progression were statistically analyzed in 40 patients with stage III colon cancer. Results: There were no statistically significant correlations between loss of membranous α -catenin and E-cadherin expressions and such variables as histologic differentiation and lymph node disease based on the criteria of the American Joint Committee on Cancer (AJCC). A significant correlation, however, existed between depth of mural invasion and loss of expressions of both α -catenin and E-cadherin (P=0.001 and P=0.002, respectively). Expressions of both α -catenin and E-cadherin were also significantly decreased in patients showing liver metastases during follow-up (P=0.019 and P=0.015, respectively). Conclusion: Immunohistochemical analyses of α -catenin and E-cadherin expressions may be available as predictors for distant metastasis, especially in stage III colon cancer. Such analyses may also help to identify appropriate therapeutic strategies and the need for intensive follow-up in patients with stage III colon cancer.

Genetics, cellular biology and tumor microenvironment of melanoma

Melanoma is an aggressive disease for which there is no effective curative treatment beyond surgical excision of the primary lesion and regional disease. Epidemiological, clinical, in vitro and in vivo studies have provided insight into the biology of the disease. This review focuses on current understanding of key molecular pathways, cellular interaction and tumor microenvironment, and the respective aberrations identified in melanoma. Common mutations and/or deregulated expressions of B-raf, N-ras, PTEN, protein kinase B (aka Akt), CDKN2A, CDK4 and MDM2 were presented. In addition to genetic abnormalities, important aspects of cellular biology including, (i) the loss of cell-cell adhesion resulting in an altered state in the relative expression of cadherins, catenins and integrins, (ii) the interaction between melanoma cells and surrounding keratinocytes, fibroblasts, and immune cells, and (iii) tumor angiogenesis and vascular mimicry, are discussed. Many ongoing clinical trials of targeted biological therapies are based on current knowledge, the outcomes are eagerly awaited.

P‐cadherin as a prognostic indicator and a modulator of migratory behaviour in bladder carcinoma cells

To identify changes associated with P-cadherin expression in bladder cancer and evaluate the potential role of such events in determining the clinical outcome and cell behaviour, as the function of P-cadherin in normal epithelium is unknown, as is its potential role in neoplastic progression in different cancers. In all, 536 bladder tumour specimens from 408 patients were assembled in seven tissue microarrays. Paraffin sections from each array were processed for immunohistochemistry to assess the expression of P-cadherin. The expression of P-cadherin was forced using lipofectin, followed by an assessment of migration and invasion potential using standard in vitro assays. The absence of P-cadherin staining was associated with muscle-invasive disease, grade 3 (P < 0.001) and nodal disease (P = 0.009). Similar results were obtained when considering cytoplasmic and unrestricted localization of P-cadherin (P < 0.001), except for nodal involvement. The group with cytoplasmic location of P-cadherin showed a shorter cancer-specific survival than the group with membrane location of P-cadherin (P = 0.03). Forced expression of P-cadherin in EJ and UM-UC-3 cells, that constitutively lack P-cadherin expression, resulted in modulation of catenin expression and enhanced migration of EJ and UM-UC-3/P-cadherin transfectants (>200%). These results showed that loss of expression, cytoplasmic relocation or unrestricted tissue location of P-cadherin was associated with a poor clinical outcome and prognosis in bladder cancer. From the in vitro work it is evident that P-cadherin plays a role in regulating the migration potential of bladder carcinoma cells.

New Advances in Breast Cancer Metastasis

New Advances in Breast Cancer Metastasis

Dog as model for down-expression of E-cadherin and β-catenin in tubular epithelial cells in renal fibrosis

Mechanism of renal fibrosis leading to end stage kidney remains still a challenge of interest in humans. The pathogenesis of chronic kidney disease is characterized by progressive loss of kidney function and fibrosis. The mechanism of epithelial-mesenchymal transition (EMT) has been predominantly studied in in vitro studies, and we previously demonstrated the EMT of tubular epithelial cells in dogs. In this study, we examined and quantified the modifications of cadherin-catenin complex by immunohistochemistry of E-cadherin and beta-catenin and the mesenchymal marker vimentin in 25 dogs with three different spontaneous inflammatory renal diseases. Results showed a significant down-expression of levels of E-cadherin and beta-catenin directly correlated with the tubular-interstitial damage (TID). In TID grades 2 and 3, E-cadherin expression was significantly reduced (p < 0.001). beta-catenin expression was overall similar to E-cadherin. The mesenchymal-associated protein, vimentin, was de novo identified in tubules within areas of inflammation. In this work, we identified the loss of cadherin or catenin expression as a progressive mechanism in tubulo-interstitial fibrosis, which allows dissociation of structural integrity of renal epithelia and loss of epithelial polarity. The dog might result more significant as model for new therapies.

Cadherin–catenin complex and transcription factor Snail-1 in spindle cell carcinoma of the head and neck

Spindle cell carcinoma (SpCC) is a biphasic tumor composed of squamous cell carcinoma (SCC) and a malignant spindle cell component. There is mounting evidence that SpCC is a monoclonal neoplasm originating from a stem cell giving rise to both components. We tested the hypothesis that spindle cell phenotype might be related to the cadherin-catenin complex, which forms adherens junctions between cells. We analyzed the immunohistochemical expression of E- and N-cadherin, alpha-, beta- and gamma-catenin, and Snail-1, a transcription repressor of E-cadherin, in 30 cases of SpCC, and 30 cases of SCC of the head and neck. In SpCC, cadherin and catenin expression was similar in the SCC component, whereas in the spindle cell component, loss of E-cadherin and neo-expression of N-cadherin was found in 19 cases, loss of cadherins in seven, and their co-expression in four cases. Catenin expression were altered in 18 SpCCs. Snail-1 was found in 19 SpCC cases. In SCC, E-cadherin and catenins were expressed in all cases, and N-cadherin focally in five cases. Snail-1 was observed in the stroma. To summarize, in SpCC, there is an altered expression of the cadherin-catenin complex, associated with morphological transition from epithelial to spindle cell phenotype. These features are reminiscent of epithelial-mesenchymal transition (EMT). Our study thus indicates that EMT might play an important role in the pathogenesis of SpCC. This conclusion is further supported by our finding of Snail-1 expression, a potent inducer of EMT, in more than half SpCC cases.

β- and γ-catenin expression in oral dysplasia

Cell-cell and cell-matrix interactions regulate important cellular functions; they involve a number of specialised molecules and the corresponding receptors, among which a key role is played by cadherins and the associated catenins. Deregulation of these molecules has been associated with tumour progression in many human malignancies. While catenins expression has been extensively studied in many human cancers, including oral carcinoma (OSCC), less is known about their expression in oral epithelial dysplasia. The objective of this study was to evaluate the expression of these proteins in a large group of displastic lesions of the oral mucosa and their relation with subsequent malignant transformation. Expression of beta- and gamma-catenin was investigated by immunohistochemistry using specific monoclonal antibodies in 49 cases of oral epithelial dysplasia and 10 samples of normal oral mucosa. The presence and absence of beta- and gamma-catenin staining was expressed differently in relation to dysplasia grade; while the degree of dysplasia became more severe, we observed a statistically significant loss and/or reduction of catenins expression, the loss of the exclusive membranous expression and a cytoplasmic delocalisation. Progression to OSCC occurred in 10 out of our 49 cases (20.4%); all of them, except one, showed a concurrent and concordantly located beta- and gamma-catenin staining even, if no statistically significant differences were found between cases progressed to invasive OSCC or not. Catenins physiology alterations may be involved in the transformation process; however, the role of catenins expression as possible prognostic markers in precancerous oral lesions seems to be limited. Nonetheless, further studies on larger series of samples are necessary in order to clarify the role of catenins expression in oral carcinogenesis from both a biological and clinical point of view.

Real time PCR analyses of expression of E-cadherin, alpha-, beta- and gamma-catenin in human breast cancer for predicting clinical outcome

BackgroundThe E-cadherin catenin system acts as an invasion suppressor of epithelial malignancies. However, it is debatable whether expression of E-cadherin or catenins is a useful prognostic marker in invasive breast cancer.MethodsWe measured the expression of E-cadherin and catenins (α-, β-, γ-catenin) in human breast carcinomas using real time quantitative polymerase chain reaction (Q-PCR) and investigated whether the expression levels were associated with known tumour variables or patient survival (median follow-up 72.2 months). RNA from frozen sections of breast tissue (tumour n = 124, background normal tissue n = 33) was reverse transcribed, quantified and analysed by Q-PCR with results expressed as number of copies of transcript/50 ng RNA.ResultsThere was no statistically significant difference in the expression of E-cadherin and catenins (α-, β-, γ-catenin)in the 33 paired normal background and tumour tissues. The expression of E-cadherin, α-, β-, and γ-catenin in node positive tumours was similar to node-negative tumours. E-cadherin, α-, β-, and γ-catenin expression in breast tumours was not related to Nottingham Prognostic Index (NPI). There was no significant difference in the expression of E-cadherin, α-, β-, γ-catenin between the various TNM stages. None of the molecular markers significantly influenced survival. Lymph node status was the only significant predictor of survival.ConclusionUsing real time quantitative PCR there was no difference in the expression of E-cadherin, α-, β-, γ-catenin between tumour and normal breast tissue. Furthermore, measurement of expression of these molecules was not of prognostic value in predicting long term outcome of women with breast cancer.

Cadherin switching dictates the biology of transitional cell carcinoma of the bladder: ex vivo and in vitro studies

Bladder cancer is the fifth most common malignancy in the UK. Clinically, the most important process in determining prognosis is the development of invasion, initially of the lamina propria and then beyond as these transitional cell carcinomas (TCCs) progress from stage pT1 to stages T2+. Cadherins and catenins are the main mediators of cell-cell interactions in epithelial tissues, and loss of membranous E-cadherin immunoreactivity is strongly correlated with high grade, advanced stage and poor prognosis in bladder cancer and other malignancies. However, the role of P-cadherin is yet to be fully elucidated in bladder TCC. The objectives of this study were to establish how the expression of cadherins and catenins determines clinical and in vitro behaviour in bladder TCC. Utilizing immunohistochemistry, immunofluorescence and western blotting, we demonstrated a significant reduction in the expression of E-cadherin and beta-catenin as grade and stage of bladder TCC progress, accompanied by a significant increase in P-cadherin expression (all p < 0.05, Pearson's chi2 test). Increased P-cadherin expression was also associated with a significantly worse bladder cancer-specific survival (log rank p = 0.008), with Cox regression showing P-cadherin to be an independent prognostic factor. Utilizing a variety of tissue culture models in a range of functional studies, we demonstrated that P-cadherin mediates defective cell-cell adhesion and enhances anchorage-independent growth. The results provide evidence that increased P-cadherin expression promotes a more malignant and invasive phenotype of bladder cancer, and appears to have a novel role late in the disease.

Breast carcinomas that co-express E- and P-cadherin are associated with p120-catenin cytoplasmic localisation and poor patient survival

Background:Changes in junctional catenin expression may compromise cadherin-mediated adhesion, increasing cell malignant properties such as invasive and metastatic abilities. Altered expression of α-, β-, γ- and p120-catenin has been reported...

Reduced expression of E-cadherin/catenin complex in hepatocellular carcinomas

To examine the immunoreactivity of E-cadherin and four subtypes of catenin family in human hepatocellular carcinomas (HCCs) and to investigate the correlation between expression of E-cadherin/catenin complex and clinicopathologic parameters of HCC patients. An immunohistochemical study for E-cadherin and catenins was performed on 97 formalin-fixed, paraffin-embedded specimens of HCC. Reduced expression of E-cadherin, alpha-, beta-, gamma-catenin and p120 was observed in 69%, 76%, 63%, 71% and 73%, respectively. Both expressions of E-cadherin and catenin components were significantly correlated with tumor grade (P = 0.000). It showed significant difference between expression of catenin members and tumor stage (P = 0.003, P = 0.017, P = 0.007 and P = 0.000, respectively). The reduced expression of E-cadherin in HCCs was significantly correlated with intrahepatic metastasis (IM) and capsular invasion (P = 0.008, P = 0.03, respectively). A close correlation was also observed between the expression of catenins and the tumor size (P = 0.002, P = 0.034, P = 0.016 and P = 0.000, respectively). In addition, the expression of each catenin was found correlated with IM (P = 0.012, P = 0.049, P = 0.026 and P = 0.014, respectively). No statistically significant difference was observed between the expression level of E-cadherin/catenin complex and lymph node permission, vascular invasion and satellite nodules. Interestingly, only expression of p120 showed correlation with AFP value (P = 0.035). The expression of E-cadherin was consistent with alpha-, beta-, gamma-catenin and p120 expression (P = 0.000). Finally, the abnormal expression of E-cadherin/catenin complex was significantly associated with patients' survival (P = 0.0253, P = 0.0052, P = 0.003, P = 0.0105 and P = 0.0016, respectively). Nevertheless, no component of E-cadherin/catenin complex was the independent prognostic factor of HCC patients. Down-regulated expressions of E-cadherin, catenins and p120 occur frequently in HCCs and contribute to the progression and development of tumor. It may be more exact and valuable to detect the co-expression of E-cadherin/catenin complex than to explore one of them in predicting tumor invasion, metastasis and patient's survival.

Intercalated disk remodeling in δ-sarcoglycan-deficient hamsters fed with an α-linolenic acid-enriched diet

Cardiomyocyte intercalated disks of delta-sarcoglycan-deficient cardiomyopathic hamsters (CMPHs) exhibit a pathological accumulation of the N-cadherin/catenin complex. CMPHs fed with an alpha-linolenic acid (ALA)-enriched diet (CMPH/FS) display an extended longevity compared to those fed with a standard diet (CMPH/PT) owing to, among others, the amelioration of both cardiac tissue structure and myocardial function. The present investigation was aimed at evaluating whether and to what extent the ALA-enriched diet affects the remodeling of CMPH cardiomyocyte intercalated disks and the expression of molecules, including N-cadherin, catenins and connexin 43 (CX43), involved in their organization. Western blot and immunohistochemical analysis demonstrated that the expression of N-cadherin, alpha- and beta-catenin is significantly reduced in cardiomyocyte intercalated disks of CMPH/FS vs. CMPH/PT and is lowered to levels similar to those found in healthy hamsters (GSH/PT), as well as transmission electron microscopy indicated that the cardiomyocyte intercalated disk ultrastructure is also re-established in CMPH/FS. In addition, the delocalization of CX43 as well as the presence of gap junctions were detectable at the lateral plasmamembrane of CMPH/FS cardiomyocytes, while the expression of myocardial CX43 was markedly reduced in both CMPH/PT and CMPH/FS, as compared to GSH/PT. Collectively, the present results demonstrate a substantial effect of an ALA-enriched diet on cardiomyocyte intercalated disk structure and molecular composition and further supports the beneficial effects of omega-3 polyunsaturated fatty acids in the prevention of potentially dangerous arrhythmias in cardiac diseases.