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plakoglobin and cancer

Aleksandra Markiewicz, Justyna Topa, Anna Nagel, Jaroslaw Skokowski, Barbara Seroczynska, Tomasz Stokowy, Marzena Welnicka-Jaskiewicz, Anna J Zaczek
Circulating tumour cells (CTCs) can provide valuable prognostic information in a number of epithelial cancers. However, their detection is hampered due to their molecular heterogeneity, which can be induced by the epithelial-mesenchymal transition (EMT) process. Therefore, current knowledge about CTCs from clinical samples is often limited due to an inability to isolate wide spectrum of CTCs phenotypes. In the current work, we aimed at isolation and molecular characterization of CTCs with different EMT status in order to establish their clinical significance in early breast cancer patients...
January 9, 2019: Cancers
Yi Sang, Longhua Sun, Yuanzhong Wu, Wenxin Yuan, Yanyan Liu, Si-Wei Li
Plakoglobin is a tumor suppressor gene in lung cancer; however, the mechanism by which it is downregulated in lung cancer is largely unknown. The aim of the present study was to investigate whether histone deacetylases (HDACs) regulate plakoglobin expression in lung cancer. The effects of overexpression or knockdown of HDAC7 on plakoglobin were determined using stably transfected lung cancer cell lines. Chromatin immunoprecipitation assays were performed to elucidate the mechanisms underlying the HDAC7‑induced suppression of plakoglobin...
January 9, 2019: International Journal of Oncology
Franziska Hoffmann, Claudia Umbreit, Thomas Krüger, Daniela Pelzel, Günther Ernst, Olaf Kniemeyer, Orlando Guntinas-Lichius, Alexander Berndt, Ferdinand von Eggeling
PURPOSE: The heterogeneity of squamous cell carcinoma tissue greatly complicates diagnosis and individualized therapy. Therefore, characterizing the heterogeneity of tissue spatially and identifying appropriate biomarkers is crucial. MALDI imaging (MSI) is capable of analyzing spatially resolved tissue biopsies on a molecular level. EXPERIMENTAL DESIGN: We used MALDI MSI on snap frozen and formalin-fixed and paraffin-embedded (FFPE) tissue samples from patients with head and neck cancer (HNC) to analyze m/z values localized in tumor and non-tumor regions...
November 9, 2018: Proteomics. Clinical Applications
Daniel T Merrick, Michael G Edwards, Wilbur A Franklin, Michio Sugita, Robert L Keith, York E Miller, Micah B Friedman, Lori D Dwyer-Nield, Meredith A Tennis, Mary C O'Keefe, Elizabeth J Donald, Jessica M Malloy, Adrie van Bokhoven, Storey Wilson, Peter J Koch, Charlene O'Shea, Christopher Coldren, David J Orlicky, Xian Lu, Anna E Baron, Greg Hickey, Timothy C Kennedy, Roger Powell, Lynn Heasley, Paul A Bunn, Mark Geraci, Raphael A Nemenoff
Persistent bronchial dysplasia is associated with increased risk of developing invasive squamous cell carcinoma (SCC) of the lung. In this study, we hypothesized that differences in gene expression profiles between persistent and regressive bronchial dysplasia would identify cellular processes that underlie progression to SCC. RNA expression arrays comparing baseline biopsies from 32 bronchial sites that persisted/progressed to 31 regressive sites showed 395 differentially expressed genes [ANOVA, FDR ≤ 0...
September 1, 2018: Cancer Research
Mahsa Alaee, Kristina Nool, Manijeh Pasdar
Tumor suppressor/transcription factor p53 is mutated in over 50% of all cancers. Some mutant p53 proteins have not only lost tumor suppressor activities but they also gain oncogenic functions (GOF). One of the most frequently expressed GOF p53 mutants is Arg175His (p53R175H ) with well-documented roles in cancer development and progression. Plakoglobin is a cell adhesion and signaling protein and a paralog of β-catenin. Unlike β-catenin that has oncogenic function through its role in the Wnt pathway, plakoglobin generally acts as a tumor/metastasis suppressor...
June 2018: Cancer Science
W Goto, S Kashiwagi, Y Asano, K Takada, K Takahashi, T Hatano, T Takashima, S Tomita, H Motomura, M Ohsawa, K Hirakawa, M Ohira
[This corrects the article DOI: 10.1186/s40364-017-0099-2.].
2018: Biomarker Research
I González-Chavarría, E Fernandez, N Gutierrez, E E González-Horta, F Sandoval, P Cifuentes, C Castillo, R Cerro, O Sanchez, Jorge R Toledo
Obesity is related to an increased risk of developing prostate cancer with high malignancy stages or metastasis. Recent results demonstrated that LOX-1, a receptor associated with obesity and atherosclerosis, is overexpressed in advanced and metastatic prostate cancer. Furthermore, high levels of oxLDL, the main ligand for LOX-1, have been found in patients with advanced prostate cancer. However, the role of LOX-1 in prostate cancer has not been unraveled completely yet. Here, we show that LOX-1 is overexpressed in prostate cancer cells and its activation by oxLDL promotes an epithelial to mesenchymal transition, through of lowered expression of epithelial markers (E-cadherin and plakoglobin) and an increased expression of mesenchymal markers (vimentin, N-cadherin, snail, slug, MMP-2 and MMP-9)...
February 1, 2018: Cancer Letters
Wataru Goto, Shinichiro Kashiwagi, Yuka Asano, Koji Takada, Katsuyuki Takahashi, Takaharu Hatano, Tsutomu Takashima, Shuhei Tomita, Hisashi Motomura, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: Circulating tumor cells (CTCs) are linked to metastatic relapse and are regarded as a prognostic marker for human cancer. High expression of plakoglobin, a cell adhesion protein, within the primary tumor is positively associated with CTC clusters in breast cancer. In this study, we investigated the correlation between plakoglobin expression and survival of breast cancer. METHODS: We evaluated 121 breast cancer patients treated with neoadjuvant chemotherapy...
2017: Biomarker Research
Ingunn Holen, Jacob Whitworth, Faith Nutter, Alyson Evans, Hannah K Brown, Diane V Lefley, Ivana Barbaric, Mark Jones, Penelope D Ottewell
No abstract text is available yet for this article.
March 28, 2017: Breast Cancer Research: BCR
Suhee Kim, Sun Hee Ahn, Hee-Young Yang, Jin-Sil Lee, Hyang-Gi Choi, Young-Kyu Park, Tae-Hoon Lee
OBJECTIVES: In tissue samples from patients with colorectal cancer (CRC), oxidation of C420 and C457 of plakoglobin (Pg) within tumor tissue was identified by proteomic analysis. The aim of this study was to identify the roles of Pg C420 and C457. METHODS: Human CRC tissues, CRC and breast cancer cells, and normal mouse colon were prepared to validate Pg oxidation. MC38 cells were co-transfected with E-cadherin plus wild type (WT) or mutant (C420S or C457S) Pg to evaluate protein interactions and cellular localization, proliferation, and migration...
November 2017: Redox Report: Communications in Free Radical Research
Idoia Ortega-Martínez, Jesús Gardeazabal, Asier Erramuzpe, Ana Sanchez-Diez, Jesús Cortés, María D García-Vázquez, Gorka Pérez-Yarza, Rosa Izu, Jose Luís Díaz-Ramón, Ildefonso M de la Fuente, Aintzane Asumendi, María D Boyano
Like many cancers, an early diagnosis of melanoma is fundamental to ensure a good prognosis, although an important proportion of stage I-II patients may still develop metastasis during follow-up. The aim of this work was to discover serum biomarkers in patients diagnosed with primary melanoma that identify those at a high risk of developing metastasis during the follow-up period. Proteomic and mass spectrophotometry analysis was performed on serum obtained from patients who developed metastasis during the first years after surgery for primary tumors and compared with that from patients who remained disease-free for more than 10 years after surgery...
October 1, 2016: International Journal of Cancer. Journal International du Cancer
Mahsa Alaee, Ghazal Danesh, Manijeh Pasdar
Aberrant expression of cadherins and catenins plays pivotal roles in ovarian cancer development and progression. Plakoglobin (PG, γ-catenin) is a paralog of β-catenin with dual adhesive and signaling functions. While β-catenin has known oncogenic function, PG generally acts as a tumor/metastasis suppressor. We recently showed that PG interacted with p53 and that its growth/metastasis inhibitory function may be mediated by this interaction. Very little is known about the role of PG in ovarian cancer. Here, we investigated the in vitro tumor/metastasis suppressor effects of PG in ovarian cancer cell lines with mutant p53 expression and different cadherin profiles...
2016: PloS One
Aswathy Ammothumkandy, Tessy Thomas Maliekal, Mayil Vahanan Bose, Thangarajan Rajkumar, Sundersingh Shirley, B Thejaswini, Venkat G Giri, Sudhir Krishna
BACKGROUND: In this study, building on our recent work identifying a subset of CD66+ve cells with distinctive tumourigenic properties in human cervical cancers, we examine patterns of expression and function of these cells; to generate insights into the process of metastasis. METHODS: Our broad approach in this study has been to compare the expression and function of two subsets marked by CD66 and CD49f. We use a combination of histopathology, immunostaining and flow cytometry, functional analysis of an established cervical cancer cell line and a retrospective analysis of a cohort of cervical cancer...
June 2016: European Journal of Cancer
Soo Shin Kim, Sujeong Yeom, Juri Kwak, Hyung-Jun Ahn, Kyung Lib Jang
Previous reports have demonstrated that hepatitis B virus (HBV) X protein (HBx) represses E-cadherin expression to induce epithelial-mesenchymal transition (EMT), an essential component of cancer progression to more aggressive phenotypes characterized by tumour invasion, migration and metastasis; however, the underlying mechanism for this phenomenon is still unclear. In this study, we found that ectopic expression of HBx in human hepatocytes using overexpression and 1.2-mer WT HBV replicon systems upregulated levels of the transcriptional repressors E12 and E47, resulting in inactivation of the E-cadherin promoter, containing three E-box motifs, and subsequent repression of its expression...
January 2016: Journal of General Virology
Kian Ngiap Chua, Li Ren Kong, Wen Jing Sim, Hsien Chun Ng, Weijie Richard Ong, Jean Paul Thiery, Hung Huynh, Boon Cher Goh
Oncogenesis in non-small cell lung cancer (NSCLC) is regulated by a complex signal transduction network. Single-agent targeted therapy fails frequently due to treatment insensitivity and acquired resistance. In this study, we demonstrate that co-inhibition of the MAPK and SRC pathways using a PD0325901 and Saracatinib kinase inhibitor combination can abrogate tumor growth in NSCLC. PD0325901/Saracatinib at 0.25:1 combination was screened against a panel of 28 NSCLC cell lines and 68% of cell lines were found to be sensitive (IC50 < 2 μM) to this combination...
October 6, 2015: Oncotarget
Otmar Huber, Iver Petersen
Desmosomes represent adhesive, spot-like intercellular junctions that in association with intermediate filaments mechanically link neighboring cells and stabilize tissue architecture. In addition to this structural function, desmosomes also act as signaling platforms involved in the regulation of cell proliferation, differentiation, migration, morphogenesis, and apoptosis. Thus, deregulation of desmosomal proteins has to be considered to contribute to tumorigenesis. Proteolytic fragmentation and downregulation of desmosomal cadherins and plaque proteins by transcriptional or epigenetic mechanisms were observed in different cancer entities suggesting a tumor-suppressive role...
2015: Cell Communication & Adhesion
Lingeng Lu, Hongmei Zeng, Xinsheng Gu, Wenxue Ma
Breast cancer recurrence is a major cause of the disease-specific death. Circulating tumor cells (CTCs) are negatively associated with breast cancer survival. Plakoglobin, a cell adhesion protein, was recently reported as a determinant of CTCs types, single or clustered ones. Here, we aim to summarize the studies on the roles of plakoglobin and evaluate the association of plakoglobin and breast cancer survival. Plakoglobin as a key component in both cell adhesion and the signaling pathways was briefly reviewed first...
June 2015: Breast Cancer Research and Treatment
Marybeth Sechler, Stanley Borowicz, Michelle Van Scoyk, Sreedevi Avasarala, Sereke Zerayesus, Michael G Edwards, Manoj Kumar Karuppusamy Rathinam, Xiangmin Zhao, Pei-Ying Wu, Ke Tang, Rama Kamesh Bikkavilli, Robert A Winn
γ-Catenin (Plakoglobin), a well-described structural protein functioning at the adherens junctions and desmosomes, was shown to be either lost or weakly expressed in non-small cell lung cancer (NSCLC) cells and tumor tissues. However, the tumor suppressive affects of γ-catenin were not fully understood. In this study, we have identified a novel role for the affects of γ-catenin on non-small cell lung cancer (NSCLC) cell migration. Expression of γ-catenin in NSCLC cells resulted in reduced cell migration as determined by both scratch assays and trans-well cell migration assays...
June 19, 2015: Journal of Biological Chemistry
Indira Tiwari, Min-Ho Yoon, Bum-Joon Park, Kyung Lib Jang
Downregulation of E-cadherin is a hallmark of epithelial-mesenchymal transition (EMT), an essential component of cancer progression to more aggressive phenotypes characterized by tumor dedifferentiation, infiltration, and metastasis. However, the underlying mechanism for E-cadherin downregulation in hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) is still unclear. In this study, we found that ectopic expression of HCV core protein or infection with HCV in human hepatocytes upregulated the levels of the transcriptional repressors, E12 and E47, resulting in inactivation of the E-cadherin promoter, containing E-box motifs, and subsequent repression of its expression...
June 28, 2015: Cancer Letters
Karina Galoian, Amir Qureshi, Gina Wideroff, H T Temple
Disruption of cell-cell junctions and the concomitant loss of polarity, downregulation of tumor-suppressive adherens junctions and desmosomes represent hallmark phenotypes for several different cancer cells. Moreover, a variety of evidence supports the argument that these two common phenotypes of cancer cells directly contribute to tumorigenesis. In this study, we aimed to determine the status of intercellular junction proteins expression in JJ012 human malignant chondrosarcoma cells and investigate the effect of the antitumorigenic cytokine, proline-rich polypeptide-1 (PRP-1) on their expression...
January 2015: Molecular and Clinical Oncology
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