Expression of the E-cadherin-catenin complex in patients with pancreatic ductal adenocarcinoma.

Pryczynicz, Anna; Guzińska‐Ustymowicz, Katarzyna; Kemonä, A; Czyżewska, Jolanta

doi:10.2478/v10042-008-0089-1

Cited by 9 publications

(10 citation statements)

References 18 publications

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“…We observed lower E-cadherin expression more frequently in male patients and higher in female patients, but there was no significant difference in survival between men and women. Contrary to our study, Pryczynicz et al did not find a correlation between E-cadherin expression and patient gender [21].…”

Section: Discussioncontrasting

confidence: 99%

“…Pećina-Šlaus et al found lower E-cadherin expression in higher-grade meningeomas [20]. Hong et al [11] also demonstrated that lower expression of E-cadherin was more common in high-grade PDAC, while Pryczynicz et al [21] did not find a correlation between E-cadherin expression and tumor grade or lymph node metastases. An in vitro study using JHP-1 adenocarcinoma cell line showed that the downregulation of E-cadherin in pancreatic carcinoma cells promoted the invasiveness into the basement membrane, and similarly in vivo selection of highly metastatic murine pancreatic cancer cells induced EMT by genetic inactivation of E-cadherin in parental cells [22,23].…”

Section: Discussionmentioning

confidence: 98%

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Immunohistochemical expression of NEDD9, E-cadherin and γ-catenin and their prognostic significance in pancreatic ductal adenocarcinoma (PDAC)

Radulović¹,

Krušlin²

2018

Bosn J of Basic Med Sci

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Extensive research is being conducted to identify novel diagnostic, predictive and prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC), as only a few markers have been routinely used so far with limited success. Our aim was to assess the expression of neural precursor cell expressed developmentally down-regulated protein 9 (NEDD9), E-cadherin, and γ-catenin in PDAC in relation to clinicopathological parameters and patient survival. We also investigated if there is a correlation of NEDD9 expression with E-cadherin or γ-catenin. The protein expression was determined by immunohistochemistry in 61 PDAC and 61 samples of normal pancreatic tissue. The log rank test and Kaplan-Meier survival curve were used for survival analysis. E-cadherin and γ-catenin expressions were reduced in PDAC, and completely retained in normal pancreatic tissue. Expression of NEDD9 was significantly increased in PDAC (strong expression in 78.7% of cases and moderate in 21.3%) and reduced in normal pancreatic tissue (strong positivity in 45.9% of cases, moderate in 31.1%, and weak in 23%). There was a positive correlation between reduced E-cadherin and γ-catenin expression in PDAC (p = 0.015). The loss or reduced expression of E-cadherin had a negative impact on patient survival (p = 0.020). A negative correlation between E-cadherin expression and tumor grade was also observed (p = 0.011). Decreased E-cadherin expression was more common in male patients with PDAC (81.3% vs. 60% for females, p = 0.005). γ-catenin and NEDD9 expressions were not statistically correlated with tumor stage and grade, gender, nor with patient survival. Our results support the role of NEDD9, E-cadherin and γ-catenin proteins in PDAC, but further research should clarify in detail their mechanism of action in pancreatic cancer.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 98%

Immunohistochemical expression of NEDD9, E-cadherin and γ-catenin and their prognostic significance in pancreatic ductal adenocarcinoma (PDAC)

Radulović¹,

Krušlin²

2018

Bosn J of Basic Med Sci

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“…Independent of the buffer no E-Cadherin expression could be detected for pancreas carcinoma and the lymph node sample. This is not astonishing as lymphocytes do not express the protein and down-regulation of E-Cadherin in pancreas carcinoma may occur [13], [14].…”

Section: Resultsmentioning

confidence: 98%

Successful Protein Extraction from Over-Fixed and Long-Term Stored Formalin-Fixed Tissues

et al. 2011

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One of the major breakthroughs in molecular pathology during the last decade was the successful extraction of full-length proteins from formalin-fixed and paraffin-embedded (FFPE) clinical tissues. However, only limited data are available for the protein extraction efficiency of over-fixed tissues and FFPE blocks that had been stored for more than 15 years in pathology archives. In this study we evaluated the protein extraction efficiency of FFPE tissues which had been formalin-fixed for up to 144 hours and tissue blocks that were stored for 20 years, comparing an established and a new commercial buffer system. Although there is a decrease in protein yield with increasing fixation time, the new buffer system allows a protein recovery of 66% from 144 hours fixed tissues compared to tissues that were fixed for 6 hours. Using the established extraction procedure, less than 50% protein recovery was seen. Similarly, the protein extraction efficiency decreases with longer storage times of the paraffin blocks. Comparing the two buffer systems, we found that 50% more proteins can be extracted from FFPE blocks that were stored for 20 years when the new buffer system is used. Taken together, our data show that the new buffer system is superior compared to the established one. Because tissue fixation times vary in the routine clinical setting and pathology archives contain billions of FFPE tissues blocks, our data are highly relevant for research, diagnosis, and treatment of disease.

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“…Absent or reduced ␣-catenin expression increases tumorigenic characteristics in vitro (37) and has been documented in esophageal, lung, stomach, pancreatic, and colorectal cancers (36,38,50). It has also been associated with metastasis (10,11).…”

Section: Discussionmentioning

confidence: 99%

DLC1 Interaction with α-Catenin Stabilizes Adherens Junctions and Enhances DLC1 Antioncogenic Activity

Tripathi

Popescu

Zimonjic

2012

Molecular and Cellular Biology

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The DLC1 (for deleted in liver cancer 1) tumor suppressor gene encodes a RhoGAP protein that inactivates Rho GTPases, which are implicated in regulation of the cytoskeleton and adherens junctions (AJs), a cell-cell adhesion protein complex associated with the actin cytoskeleton. Malignant transformation and tumor progression to metastasis are often associated with changes in cytoskeletal organization and cell-cell adhesion. Here we have established in human cells that the AJ-associated protein ␣-catenin is a new binding partner of DLC1. Their binding was mediated by the N-terminal amino acids 340 to 435 of DLC1 and the N-terminal amino acids 117 to 161 of ␣-catenin. These proteins colocalized in the cytosol and in the plasma membrane, where together they associated with E-cadherin and ␤-catenin, constitutive AJ proteins. Binding of DLC1 to ␣-catenin led to their accumulation at the plasma membrane and required DLC1 GAP activity. Knocking down ␣-catenin in DLC1-positive cells diminished DLC1 localization at the membrane. The DLC1-␣-catenin complex reduced the Rho GTP level at the plasma membrane, increased E-cadherin's mobility, affected actin organization, and stabilized AJs. This process eventually contributed to a robust oncosuppressive effect of DLC1 in metastatic prostate carcinoma cells. Together, these results unravel a new mechanism through which DLC1 exerts its strong oncosuppressive function by positively influencing AJ stability. Cancer initiation and progression constitute a multistep process, associated with both structural changes in certain genes and alterations in the dynamics and magnitude of their expression. Mutations and various chromosome rearrangements can invariably change the nature of the gene-encoded message; different molecular interactions and epigenetic modifications can modulate gene expression. Accumulation of genetic and epigenetic abnormalities results in the appearance of deviant cells refractory to normal homeostatic regulatory mechanisms and with a newly acquired capacity for unlimited, self-sufficient proliferation (6,20).Activation of oncogenes and/or inactivation of tumor suppressor genes (TSG) is often associated with a neoplastic phenotype. Over the past few years, the DLC1 gene, encoding a Rho GTPaseactivating protein (RhoGAP), has been established as a genuine TSG and increasingly considered a metastasis suppressor gene in various cancers. Aberrant upregulation of Rho GTPases is a major factor in the neoplastic process and tumor progression to metastasis (13). DLC1 plays a key role in regulation of actin cytoskeleton and focal adhesions, in the process of cell migration and invasion, tumor cell dissemination, and metastasis, and in programmed cell death and neoangiogenesis (13,16,19,26,39,49,64,69). DLC1 has been shown to be one of the most frequently inactivated TSGs, predominantly by epigenetic modifications (13,29,30,58,60,66). Restoration of DLC1 expression in various carcinomas and in multiple myeloma cell lines results in suppression of proliferation, tumorigenicit...

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Expression of the E-cadherin-catenin complex in patients with pancreatic ductal adenocarcinoma.

Cited by 9 publications

References 18 publications

Immunohistochemical expression of NEDD9, E-cadherin and γ-catenin and their prognostic significance in pancreatic ductal adenocarcinoma (PDAC)

Immunohistochemical expression of NEDD9, E-cadherin and γ-catenin and their prognostic significance in pancreatic ductal adenocarcinoma (PDAC)

Successful Protein Extraction from Over-Fixed and Long-Term Stored Formalin-Fixed Tissues

DLC1 Interaction with α-Catenin Stabilizes Adherens Junctions and Enhances DLC1 Antioncogenic Activity

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