المؤلفون: Razan Abou Ziki, Sabine Colnot

المصدر: JHEP Reports, Vol 6, Iss 5, Pp 101077- (2024)

مصطلحات موضوعية: Hepatocellular carcinoma, beta-catenin, glutamine metabolism, glutaminase, glutamine synthetase, liver zonation, Diseases of the digestive system. Gastroenterology, RC799-869

الوصف: Summary: The reprogramming of glutamine metabolism is a key event in cancer more generally and in hepatocellular carcinoma (HCC) in particular. Glutamine consumption supplies tumours with ATP and metabolites through anaplerosis of the tricarboxylic acid cycle, while glutamine production can be enhanced by the overexpression of glutamine synthetase. In HCC, increased glutamine production is driven by activating mutations in the CTNNB1 gene encoding β-catenin. Increased glutamine synthesis or utilisation impacts tumour epigenetics, oxidative stress, autophagy, immunity and associated pathways, such as the mTOR (mammalian target of rapamycin) pathway. In this review, we will discuss studies which emphasise the pro-tumoral or tumour-suppressive effect of glutamine overproduction. It is clear that more comprehensive studies are needed as a foundation from which to develop suitable therapies targeting glutamine metabolic pathways, depending on the predicted pro- or anti-tumour role of dysregulated glutamine metabolism in distinct genetic contexts.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2589555924000818Test; https://doaj.org/toc/2589-5559Test

الوصول الحر: https://doaj.org/article/3cfce426e10441f1a98e4e2a252c897bTest

المؤلفون: Caroline Gest, Sandra Sena, Lydia Dif, Véronique Neaud, Robin Loesch, Nathalie Dugot-Senant, Lisa Paysan, Léo Piquet, Terezinha Robbe, Nathalie Allain, Doulaye Dembele, Catherine Guettier, Paulette Bioulac-Sage, Anne Rullier, Brigitte Le Bail, Christophe F. Grosset, Frédéric Saltel, Valérie Lagrée, Sabine Colnot, Violaine Moreau

المصدر: JHEP Reports, Vol 5, Iss 5, Pp 100691- (2023)

مصطلحات موضوعية: Hepatoblastoma, Differentiation, Beta-catenin, Fascin-1, Diseases of the digestive system. Gastroenterology, RC799-869

الوصف: Background & Aims: β-catenin is a well-known effector of the Wnt pathway, and a key player in cadherin-mediated cell adhesion. Oncogenic mutations of β-catenin are very frequent in paediatric liver primary tumours. Those mutations are mostly heterozygous, which allows the co-expression of wild-type (WT) and mutated β-catenins in tumour cells. We investigated the interplay between WT and mutated β-catenins in liver tumour cells, and searched for new actors of the β-catenin pathway. Methods: Using an RNAi strategy in β-catenin-mutated hepatoblastoma (HB) cells, we dissociated the structural and transcriptional activities of β-catenin, which are carried mainly by WT and mutated proteins, respectively. Their impact was characterised using transcriptomic and functional analyses. We studied mice that develop liver tumours upon activation of β-catenin in hepatocytes (APCKO and β-cateninΔexon3 mice). We used transcriptomic data from mouse and human HB specimens, and used immunohistochemistry to analyse samples. Results: We highlighted an antagonistic role of WT and mutated β-catenins with regard to hepatocyte differentiation, as attested by alterations in the expression of hepatocyte markers and the formation of bile canaliculi. We characterised fascin-1 as a transcriptional target of mutated β-catenin involved in tumour cell differentiation. Using mouse models, we found that fascin-1 is highly expressed in undifferentiated tumours. Finally, we found that fascin-1 is a specific marker of primitive cells including embryonal and blastemal cells in human HBs. Conclusions: Fascin-1 expression is linked to a loss of differentiation and polarity of hepatocytes. We present fascin-1 as a previously unrecognised factor in the modulation of hepatocyte differentiation associated with β-catenin pathway alteration in the liver, and as a new potential target in HB. Impact and implications: The FSCN1 gene, encoding fascin-1, was reported to be a metastasis-related gene in various cancers. Herein, we uncover its expression in poor-prognosis hepatoblastomas, a paediatric liver cancer. We show that fascin-1 expression is driven by the mutated beta-catenin in liver tumour cells. We provide new insights on the impact of fascin-1 expression on tumour cell differentiation. We highlight fascin-1 as a marker of immature cells in mouse and human hepatoblastomas.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2589555923000228Test; https://doaj.org/toc/2589-5559Test

الوصول الحر: https://doaj.org/article/842490d9fd564a5d9087b3a228132176Test

المؤلفون: Michael J. Theiss, Sarah H. Glass, Robert A. Strauss, Daniel M. Laskin

المصدر: Oral and Maxillofacial Surgery Cases, Vol 8, Iss 3, Pp 100270- (2022)

مصطلحات موضوعية: Peripheral dentinogenic ghost cell tumor, Beta-catenin staining, Local excision, Surgery, RD1-811

الوصف: The peripheral dentinogenic ghost cell tumor (PDGCT) is a locally invasive odontogenic tumor that represents 0.3–0.5% of all odontogenic tumors. These lesions may mimic the clinical presentation of several other soft tissue tumors that are more commonly seen. This case report describes a case of PDGCT in a 71-year-old male and reviews the literature associated with the diagnosis, histology, and management of these lesions.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2214541922000293Test; https://doaj.org/toc/2214-5419Test

الوصول الحر: https://doaj.org/article/ae689dcc511a43a1bf1bb81428eb8b66Test

المؤلفون: Christopher M. Chandler, Kevin P. Labadie, James O. Park, Camtu D. Truong

المصدر: Human Pathology: Case Reports, Vol 24, Iss , Pp 200501- (2021)

مصطلحات موضوعية: Hepatic adenoma, Hepatocellular carcinoma, Beta-catenin activation, Inflammatory hepatic adenoma, Malignant transformation, Pathology, RB1-214

الوصف: Hepatic adenomas are benign but carry risk of hemorrhage and malignant transformation, the latter complication being more common in those with β-catenin mutations. We report a case of hepatocellular carcinoma arising in a large inflammatory hepatic adenoma (9.2 cm) with β-catenin mutation. Gross pathology, radiology, and histopathology are shown. This case highlights the risk of malignant transformation that accompanies large tumor size, β-catenin activation, and reinforces the need for surgical intervention in such cases.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2214330021000304Test; https://doaj.org/toc/2214-3300Test

الوصول الحر: https://doaj.org/article/5ab07763752043daa9952d339da81827Test

المؤلفون: Devrim Kahraman, Berkem Karakoyunlu, Ulker Karagece, Umit Ertas, Omer Gunhan

المصدر: Journal of Bone Oncology, Vol 26, Iss , Pp 100333- (2021)

مصطلحات موضوعية: Desmoplastic fibroma, Jaw bones, Nestin, Beta-catenin, Neural crest, Fibromatosis, Diseases of the musculoskeletal system, RC925-935, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Desmoplastic fibroma (DF) is an intraosseous counterpart of desmoid-type soft tissue fibromatosis. It is most frequently seen in the jawbones. The clinical and radiological features of the present cases were nonspecific. The accumulation of beta-catenin in the nuclei of neoplastic cells which is a diagnostic feature of desmoid-type soft tissue fibromatosis could not be detectED in the present DF series. The aim of this study is to report a series of 22 cases of DF involving either mandible or maxilla. A retrospective evaluation of desmoplastic fibroma and beta-catenin, smooth muscle actin, nestin, cyclin D1 immunostaining’s patterns.Most of the DF cases expressed only cytoplasmic beta-catenin immunostainings. We suggest that nuclear beta-catenin staining may not be used as a corroborating the diagnosis of DF. Immunohistochemical staining difference of jaw bone desmoplastic fibromas from other soft tissue and bone lesions may be related to the origination of jaw bone from The neural crest. Strong nestin and cyclin D1 positivity in our series supported this. A combined clinical, radiological, and histopathological analysis of the DF cases is essential in the diagnosis and management.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2212137420300889Test; https://doaj.org/toc/2212-1374Test

الوصول الحر: https://doaj.org/article/43fc244ee10a4937b62fdd39d92ef241Test

المؤلفون: Bee Ling Tan, Mohd Esa Norhaizan

المصدر: Biomedicine & Pharmacotherapy, Vol 110, Iss , Pp 748-757 (2019)

مصطلحات موضوعية: Apoptosis, Beta-catenin, Caspase-dependent pathway, Cytotoxicity, Manilkara zapota, Therapeutics. Pharmacology, RM1-950

الوصف: Manilkara zapota (L.) P. Royen (Family: Sapotaceae), commonly called as sapodilla, has been applied as traditional folk medicine for diarrhea and pulmonary infections. Conventional therapy in colorectal cancer is not likely effective due to undesirable outcomes. The anti-colon cancer properties of Manilkara zapota leaf water extract have yet to be investigated thus far. Therefore, our present study aimed to evaluate the ability to induce apoptosis and the underlying mechanisms of Manilkara zapota leaf water extract against human colorectal cancer (HT-29) cells. The cytotoxicity of Manilkara zapota leaf water extract was screened in different cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) analyses. The morphological changes in HT-29 cell lines after exposure to Manilkara zapota leaf water extract were viewed under fluorescence and inverted light microscope. The apoptotic cell was measured by Annexin V-propidium iodide staining. The caspase-3 and -8 activities were assessed by colorimetric assay. Overall analyses revealed that treatment with Manilkara zapota leaf water extract for 72 h can inhibit the viability of HT-29 cells. Incubation with Manilkara zapota leaf water extract for 24, 48, and 72 h significantly increased (p < 0.05) the total apoptotic cells compared to the control. Treatment with 21, 42, and 84 μg/mL of Manilkara zapota leaf water extract for 72 h triggered both caspase-3 and -8 activities in a concentration-dependent pattern. We also found that the catalase level in the two treatment groups (21 and 42 μg/mL) was significantly elevated after 24 h incubation. Incubation with Manilkara zapota leaf water extract for 72 h triggered the transcriptional elevation of the adenomatous polyposis coli (APC), glycogen synthase kinase 3β (GSK3β), AXIN1, and casein kinase 1 (CK1). The β-catenin mRNA levels were reduced accordingly when the concentration of the Manilkara zapota leaf water extract was increased. Our results suggested that Manilkara zapota leaf water extract offer great potential against colorectal cancer through modulation of Wnt/β-catenin signaling pathway, caspase-dependent pathway, and antioxidant enzyme.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S075333221834349XTest; https://doaj.org/toc/0753-3322Test

الوصول الحر: https://doaj.org/article/032058e82ac24a259a606132dacffab9Test

المؤلفون: Stewart W.C. Masson, Brie Sorrenson, Peter R. Shepherd, Troy L. Merry

المصدر: Molecular Metabolism, Vol 42, Iss , Pp 101091- (2020)

مصطلحات موضوعية: Beta-catenin, Actin-remodelling, Glucose transport, M-cadherin, GLUT4 trafficking, Internal medicine, RC31-1245

الوصف: Objective: Skeletal muscle glucose disposal following a meal is mediated through insulin-stimulated movement of the GLUT4-containing vesicles to the cell surface. The highly conserved scaffold-protein β-catenin is an emerging regulator of vesicle trafficking in other tissues. Here, we investigated the involvement of β-catenin in skeletal muscle insulin-stimulated glucose transport. Methods: Glucose homeostasis and transport was investigated in inducible muscle specific β-catenin knockout (BCAT-mKO) mice. The effect of β-catenin deletion and mutation of β-catenin serine 552 on signal transduction, glucose uptake and protein–protein interactions were determined in L6-G4-myc cells, and β-catenin insulin-responsive binding partners were identified via immunoprecipitation coupled to label-free proteomics. Results: Skeletal muscle specific deletion of β-catenin impaired whole-body insulin sensitivity and insulin-stimulated glucose uptake into muscle independent of canonical Wnt signalling. In response to insulin, β-catenin was phosphorylated at serine 552 in an Akt-dependent manner, and in L6-G4-myc cells, mutation of β-cateninS552 impaired insulin-induced actin-polymerisation, resulting in attenuated insulin-induced glucose transport and GLUT4 translocation. β-catenin was found to interact with M-cadherin in an insulin-dependent β-cateninS552-phosphorylation dependent manner, and loss of M-cadherin in L6-G4-myc cells attenuated insulin-induced actin-polymerisation and glucose transport. Conclusions: Our data suggest that β-catenin is a novel mediator of glucose transport in skeletal muscle and may contribute to insulin-induced actin-cytoskeleton remodelling to support GLUT4 translocation.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2212877820301654Test; https://doaj.org/toc/2212-8778Test

الوصول الحر: https://doaj.org/article/be0ebe21d60544d69a6c52ffdbaef546Test

المؤلفون: Suzy M Scholl, Jonas Beal, Leanne de Koning, Elodie Girard, Marina Popovic, Anne de la Rochefordière, Fabrice Lecuru, Virginie Fourchotte, Charlotte Ngo, Anne Floquet, Els MJJ Berns, Gemma Kenter, Pierre Gestraud, Heiko von der Leyen, Charlotte Lecerf, Vincent Puard, Sergio Roman Roman, Aurelien Latouche, Attila Kereszt, Balazs Balint, Roman Rouzier, Maud Kamal

المصدر: EBioMedicine, Vol 61, Iss , Pp 103049- (2020)

مصطلحات موضوعية: Cervical cancer, Molecular landscape, Molecular and protein biomarkers for chemo-radiation efficiency, Beta-catenin pβ-cat552 and pβ-cat675, Medicine, Medicine (General), R5-920

الوصف: ABSTRACT: BACKGROUND: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality world wide and constitutes the third most common malignancy in women. The RAIDs consortium (http://www.raids-fp7.euTest/) conducted a prospective European study [BioRAIDs (NCT02428842)] with the objective to stratify CC patients for innovative treatments. A “metagene” of genomic markers in the PI3K pathway and epigenetic regulators had been previously associated with poor outcome [2]. METHODS: To detect new, more specific, targets for treatment of patients who resist standard chemo-radiation, a high-dimensional Cox model was applied to define dominant molecular variants, copy number variations, and reverse phase protein arrays (RPPA). FINDINGS: Survival analysis on 89 patients with all omics data available, suggested loss-of-function (LOF) or activating molecular alterations in nine genes to be candidate biomarkers for worse prognosis in patients treated by chemo-radiation while LOF of ATRX, MED13 as well as CASP8 were associated with better prognosis. When protein expression data by RPPA were factored in, the supposedly low molecular weight and nuclear form, of beta-catenin, phosphorylated in Ser552 (pβ-Cat552), ranked highest for good prognosis, while pβ-Cat675 was associated with worse prognosis. INTERPRETATION: These findings call for molecularly targeted treatments involving p53, Wnt pathway, PI3K pathway, and epigenetic regulator genes. Pβ-Cat552 and pβ-Cat675 may be useful biomarkers to predict outcome to chemo-radiation, which targets the DNA repair axis. FUNDING: European Union's Seventh Program for research, technological development and demonstration (agreement N°304,810), the Fondation ARC pour la recherche contre le cancer.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2352396420304254Test; https://doaj.org/toc/2352-3964Test

الوصول الحر: https://doaj.org/article/cfe26dbac59448418117b813f389a650Test

المؤلفون: Scholl, Suzy M, Beal, Jonas, de Koning, Leanne, Girard, Elodie, Popovic, Marina, de La Rochefordière, Anne, Lecuru, Fabrice, Fourchotte, Virginie, Ngo, Charlotte, Floquet, Anne, Berns, Els Mjj, Kenter, Gemma, Gestraud, Pierre, von Der Leyen, Heiko, Lecerf, Charlotte, Puard, Vincent, Roman, Sergio Roman, Latouche, Aurelien, Kereszt, Attila, Balint, Balazs, Rouzier, Roman, Kamal, Maud

المساهمون: Université Paris Sciences et Lettres (PSL), Institut Curie Paris, Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut Curie Paris -Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou APHP (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), Institut Bergonié Bordeaux, UNICANCER, Erasmus University Medical Center Rotterdam (Erasmus MC), Amsterdam UMC - Amsterdam University Medical Center, Netherlands Cancer Institute (NKI), Antoni van Leeuwenhoek Hospital, Medizinische Hochschule Hannover = Hannover Medical School (MHH), Conservatoire National des Arts et Métiers CNAM (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Centre d'études et de recherche en informatique et communications (CEDRIC), Ecole Nationale Supérieure d'Informatique pour l'Industrie et l'Entreprise (ENSIIE)-Conservatoire National des Arts et Métiers CNAM (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Enterprise SeqOmics Biotechnology Ltd, Partenaires INRAE

المصدر: ISSN: 2352-3964 ; EBioMedicine ; https://hal.science/hal-03492821Test ; EBioMedicine, 2020, 61, pp.103049. ⟨10.1016/j.ebiom.2020.103049⟩.

مصطلحات موضوعية: Beta-catenin pβ-cat552 and pβ-cat675, Cervical cancer, Molecular and protein biomarkers for chemo-radiation efficiency, Molecular landscape, [SDV]Life Sciences [q-bio]

الوصف: International audience ; Background: Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality world wide and constitutes the third most common malignancy in women. The RAIDs consortium (http://www.raids-fp7.euTest/) conducted a prospective European study [BioRAIDs (NCT02428842)] with the objective to stratify CC patients for innovative treatments. A "metagene" of genomic markers in the PI3K pathway and epigenetic regulators had been previously associated with poor outcome [2].Methods: To detect new, more specific, targets for treatment of patients who resist standard chemo-radiation, a high-dimensional Cox model was applied to define dominant molecular variants, copy number variations, and reverse phase protein arrays (RPPA).Findings: Survival analysis on 89 patients with all omics data available, suggested loss-of-function (LOF) or activating molecular alterations in nine genes to be candidate biomarkers for worse prognosis in patients treated by chemo-radiation while LOF of ATRX, MED13 as well as CASP8 were associated with better prognosis. When protein expression data by RPPA were factored in, the supposedly low molecular weight and nuclear form, of beta-catenin, phosphorylated in Ser552 (pβ-Cat552), ranked highest for good prognosis, while pβ-Cat675 was associated with worse prognosis.Interpretation: These findings call for molecularly targeted treatments involving p53, Wnt pathway, PI3K pathway, and epigenetic regulator genes. Pβ-Cat552 and pβ-Cat675 may be useful biomarkers to predict outcome to chemo-radiation, which targets the DNA repair axis.Funding: European Union's Seventh Program for research, technological development and demonstration (agreement N°304,810), the Fondation ARC pour la recherche contre le cancer.

العلاقة: info:eu-repo/semantics/altIdentifier/pmid/33096476; hal-03492821; https://hal.science/hal-03492821Test; https://hal.science/hal-03492821/documentTest; https://hal.science/hal-03492821/file/S2352396420304254.pdfTest; PII: S2352-3964(20)30425-4; PUBMED: 33096476; PUBMEDCENTRAL: PMC7581879

الإتاحة: https://doi.org/10.1016/j.ebiom.2020.103049Test
https://hal.science/hal-03492821Test
https://hal.science/hal-03492821/documentTest
https://hal.science/hal-03492821/file/S2352396420304254.pdfTest

المؤلفون: Prieto, Ignacio, Rubio Alarcón, Carmen, García Gómez, Raquel, Berdún, Rebeca, Urgel, Tamara, Portero, Manuel, Pamplona, Reinald, Martínez Ruiz, Antonio, Ruiz Sanz, José Ignacio, Ruiz Larrea, María Begoña, Jove, Mariona, Cerdán, Sebastián, Monsalve, María

المساهمون: European Commission

مصطلحات موضوعية: PGC-1 alpha, metabolism, cancer, tumor, metastasis:cancer-cell metabolism, mitochondrial metabolism, c-myc, glutamine-metabolism, beta-catenin, amino-acid, reductive carboxylation, expression, inhibition

الوصف: PGC-1 alpha controls, to a large extent, the capacity of cells to respond to changing nutritional requirements and energetic demands. The key role of metabolic reprogramming in tumor development has highlighted the potential role of PGC-1 alpha in cancer. To investigate how loss of PGC-1 alpha activity in primary cells impacts the oncogenic characteristics of spontaneously immortalized cells, and the mechanisms involved, we used the classic 3T3 protocol to generate spontaneously immortalized mouse embryonic fibroblasts (iMEFs) from wild-type (WT) and PGC-1 alpha knockout (KO) mice and analyzed their oncogenic potential in vivo and in vitro. We found that PGC-1 alpha KO iMEFs formed larger and more proliferative primary tumors than WT counterparts, and fostered the formation of lung metastasis by B16 melanoma cells. These characteristics were associated with the reduced capacity of KO iMEFs to respond to cell contact inhibition, in addition to an increased ability to form colonies in soft agar, an enhanced migratory capacity, and a reduced growth factor dependence. The mechanistic basis of this phenotype is likely associated with the observed higher levels of nuclear beta-catenin and c-myc in KO iMEFs. Evaluation of the metabolic adaptations of the immortalized cell lines identified a decrease in oxidative metabolism and an increase in glycolytic flux in KO iMEFs, which were also more dependent on glutamine for their survival. Furthermore, glucose oxidation and tricarboxylic acid cycle forward flux were reduced in KO iMEF, resulting in the induction of compensatory anaplerotic pathways. Indeed, analysis of amino acid and lipid patterns supported the efficient use of tricarboxylic acid cycle intermediates to synthesize lipids and proteins to support elevated cell growth rates. All these characteristics have been observed in aggressive tumors and support a tumor suppressor role for PGC-1 alpha, restraining metabolic adaptations in cancer. ; This work was funded by grants from the Spanish "Ministerio de Ciencia, ...

وصف الملف: application/pdf

العلاقة: info:eu-repo/grantAgreement/EC/H2020/721236; https://www.sciencedirect.com/science/article/pii/S2213231719308742?via%3DihubTest; Redox Biology 29 : (2020) // Article ID UNSP 101396; http://hdl.handle.net/10810/43472Test

الإتاحة: https://doi.org/10.1016/j.redox.2019.101396Test
http://hdl.handle.net/10810/43472Test