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Your search keyword '"Maria Annunziata Carella"' showing total 2 results
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2 results on '"Maria Annunziata Carella"'

1. High Expression of Glycolytic Genes in Cirrhosis Correlates With the Risk of Developing Liver Cancer

Author

Nathan C. W. Lee, Maria Annunziata Carella, Salvatore Papa, and Concetta Bubici

Subjects
glucose metabolism, aerobic glycolysis, the Warburg effect, liver, liver cancer, Biology (General), QH301-705.5
Abstract

A marked increase in the rate of glycolysis is a key event in the pathogenesis of hepatocellular carcinoma (HCC), the main type of primary liver cancer. Liver cirrhosis is considered to be a key player in HCC pathogenesis as it precedes HCC in up to 90% of patients. Intriguingly, the biochemical events that underlie the progression of cirrhosis to HCC are not well understood. In this study, we examined the expression profile of metabolic gene transcripts in liver samples from patients with HCC and patients with cirrhosis. We found that gene expression of glycolytic enzymes is up-regulated in precancerous cirrhotic livers and significantly associated with an elevated risk for developing HCC. Surprisingly, expression levels of genes involved in mitochondrial oxidative metabolism are markedly increased in HCC compared to normal livers but remain unchanged in cirrhosis. Our findings suggest that key glycolytic enzymes such as hexokinase 2 (HK2), aldolase A (ALDOA), and pyruvate kinase M2 (PKM2) may represent potential markers and molecular targets for early detection and chemoprevention of HCC.

Published
2018
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2. Phosphorylation and stabilization of PIN1 by JNK promote intrahepatic cholangiocarcinoma growth

Author

Concetta Bubici, Shannon Glaser, Clive D'Santos, Rosy Favicchio, Wing-Kin Syn, Georgios Giamas, PM Choy, Alessio Lepore, Mihaela Lorger, Maria Annunziata Carella, Marco A. Briones-Orta, Reuben Tooze, Nathan C. W. Lee, Salvatore Papa, Athanasios Papakyriakou, Gianfranco Alpini, Alpini, Gianfranco [0000-0002-6658-3021], Papakyriakou, Athanasios [0000-0003-3931-6232], Giamas, Georgios [0000-0002-4417-2707], Bubici, Concetta [0000-0002-8074-4661], Papa, Salvatore [0000-0002-8369-6538], and Apollo - University of Cambridge Repository

Subjects
C-JUN, Carcinogenesis, oncogenes, trans-retinoic acid, c-jun, isomerase pin1, Mice, SCID, in-vivo, Cholangiocarcinoma, Blood cancer, Mice, ISOMERASE PIN1, Mice, Inbred NOD, Phosphorylation, RNA, Small Interfering, IN-VIVO, Intrahepatic Cholangiocarcinoma, degradation, Tumor Burden, Management, 1101 Medical Biochemistry and Metabolomics, 1107 Immunology, Gene Knockdown Techniques, frequency, Posttranslational modification, Female, Life Sciences & Biomedicine, MAP Kinase Signaling System, Antineoplastic Agents, Tretinoin, UBIQUITINATION, FREQUENCY, ubiquitination, Research initiative, bile duct cancer, Cell Line, Tumor, Political science, ubiquitin, Animals, Humans, Mitogen-Activated Protein Kinase 9, BREAST-CANCER, cancer, Mitogen-Activated Protein Kinase 8, breast-cancer, Science & Technology, Gastroenterology & Hepatology, Hepatology, MUTATIONS, transformation, 1103 Clinical Sciences, DEGRADATION, mutations, Xenograft Model Antitumor Assays, TRANSFORMATION, NIMA-Interacting Peptidylprolyl Isomerase, TRANS-RETINOIC ACID, Bile Duct Neoplasms, post-translational modification
Abstract

Supporting information is available online at https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.31983#support-information-section . From 2023 Hepatology is published by Wolters Kluwer Health on behalf of the American Association for the Study of Liver Diseases. Background and Aims Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive type of liver cancer in urgent need of treatment options. Aberrant activation of c-Jun N-terminal kinase (JNK) pathway is a key feature in ICC and an attractive candidate target for its treatment. However, the mechanisms by which constitutive JNK activation promotes ICC growth, and thus the key downstream effectors of this pathway remain unknown for their applicability as therapeutic targets. Our aim was to obtain a better mechanistic understanding of the role of JNK signalling in ICC that could open new therapeutic opportunities. Approach and Results Using loss- and gain-of-function studies in vitro and in vivo, we show that activation of the JNK pathway promotes ICC cell proliferation by affecting the protein stability of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), a key driver of tumorigenesis. PIN1 is highly expressed in ICC primary tumours, and its expression positively correlates with active JNK. Mechanistically, the JNK kinases directly bind to and phosphorylate PIN1 at Ser115, and this phosphorylation prevents PIN1 mono-ubiquitination at Lys117 and its proteasomal degradation. Moreover, pharmacological inhibition of PIN1 via all-trans retinoic acid (ATRA), an FDA-approved drug, impairs the growth of both cultured and xenografted ICC cells. Conclusions Our findings implicate the JNK-PIN1 regulatory axis as a functionally important determinant for ICC growth, and provide a rationale for therapeutic targeting of JNK activation via PIN1 inhibition. AMMF - The Cholangiocarcinoma Charity. Grant Number: 2014; Foundation for Liver Research. Grant Number: Start-up 2010; Guts UK. Grant Number: DGO2019_02; Rosetrees Trust. Grant Number: M894; Brunel University London. Grant Number: BRIEF LBL348; Blood Cancer UK. Grant Number: 17014; Faculty of Medicine and Health, University of Leeds. Grant Number: 250 ; Great Minds University Academic Fellowship 2016.

Published
2021

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