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Cancers
Special Issues
Signaling Pathways Involved in Liver Cancer Development and Progression
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Signaling Pathways Involved in Liver Cancer Development and Progression

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (1 May 2022) | Viewed by 9846

Special Issue Editor

Dr. Alessandra Gentilini

E-Mail Website
Guest Editor
Department of Experimental and Clinical Medicine, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy
Interests: adjustment of expression of the platelet-derived growth factor (PDGF) subunits by the transforming growth factor-beta 1 (TGF-β1) in human CSP; expression and pathophysiologic-prognostic role of expression of the platelet-derived growth factor and its relative subunits undergoing active liver fibrogenesis; role of the activation of phosphatidylinositol 3- (PI 3-) kinase in mitogenesis and chemotaxis induced by platelet-derived growth factor in human CSP; adjustment of gene expression for type 1 procollagen by lipid-peroxidative mechanisms and reactive human aldehyde CSPs; expression of endothelin-1 (ET-1) in the human and cirrhotic liver and biological effects of ET-1 in human CSP; characterization and regulation of insulin-like growth factor binding proteins (IGFBPs) in human CSPs

Special Issue Information

Dear Colleagues,

Signaling pathways play an essential role in cancer development and progression. Most pathways result in deregulation in tumor cells, triggering a proliferative and aggressive phenotype. Several pathways have been linked to liver tumor progression, as PI3K/AKT, MAPKs, TGF β, Notch, Wnt/β-catenin, Hippo and apoptotic signaling. Signaling proteins and soluble factors/receptors that modulate these pathways are potential targets for therapeutic treatments. To date, only a limited number of drugs have successfully been employed in liver cancer therapies, for different reasons, including the high heterogeneity of tumors and a still limited knowledge of signaling cascades and their crosstalk. Nevertheless, as research goes on, new findings are emerging, and novel drugs developed. At present, a number of clinical trials have been conducting for testing agents that act on growth factor receptors and intracellular signaling pathways.

Thus, it could be useful to provide insight into the molecular mechanisms leading to liver development and progression, and eventually, potential therapeutic treatments for patients affected by liver cancer.

Dr. Alessandra Gentilini
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • signaling pathways
  • liver cancer
  • cancer progression
  • target therapies
  • molecular mechanisms
  • signaling cascades crosstalk

Published Papers (3 papers)

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Research

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21 pages, 6979 KiB  
Article
Optimization and Validation of a Novel Three-Dimensional Co-Culture System in Decellularized Human Liver Scaffold for the Study of Liver Fibrosis and Cancer
by Kessarin Thanapirom, Elisabetta Caon, Margarita Papatheodoridi, Luca Frenguelli, Walid Al-Akkad, Zhang Zhenzhen, Maria Giovanna Vilia, Massimo Pinzani, Giuseppe Mazza and Krista Rombouts
Cancers 2021, 13(19), 4936; https://doi.org/10.3390/cancers13194936 - 30 Sep 2021
Cited by 13 | Viewed by 3005
Abstract
The introduction of new preclinical models for in vitro drug discovery and testing based on 3D tissue-specific extracellular matrix (ECM) is very much awaited. This study was aimed at developing and validating a co-culture model using decellularized human liver 3D ECM scaffolds as [...] Read more.
The introduction of new preclinical models for in vitro drug discovery and testing based on 3D tissue-specific extracellular matrix (ECM) is very much awaited. This study was aimed at developing and validating a co-culture model using decellularized human liver 3D ECM scaffolds as a platform for anti-fibrotic and anti-cancer drug testing. Decellularized 3D scaffolds obtained from healthy and cirrhotic human livers were bioengineered with LX2 and HEPG2 as single and co-cultures for up to 13 days and validated as a new drug-testing platform. Pro-fibrogenic markers and cancer phenotypic gene/protein expression and secretion were differently affected when single and co-cultures were exposed to TGF-β1 with specific ECM-dependent effects. The anti-fibrotic efficacy of Sorafenib significantly reduced TGF-β1-induced pro-fibrogenic effects, which coincided with a downregulation of STAT3 phosphorylation. The anti-cancer efficacy of Regorafenib was significantly reduced in 3D bioengineered cells when compared to 2D cultures and dose-dependently associated with cell apoptosis by cleaved PARP-1 activation and P-STAT3 inhibition. Regorafenib reversed TGF-β1-induced P-STAT3 and SHP-1 through induction of epithelial mesenchymal marker E-cadherin and downregulation of vimentin protein expression in both co-cultures engrafting healthy and cirrhotic 3D scaffolds. In their complex, the results of the study suggest that this newly proposed 3D co-culture platform is able to reproduce the natural physio-pathological microenvironment and could be employed for anti-fibrotic and anti-HCC drug screening. Full article
(This article belongs to the Special Issue Signaling Pathways Involved in Liver Cancer Development and Progression)
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Review

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14 pages, 1177 KiB  
Review
Oncostatin M: From Intracellular Signaling to Therapeutic Targets in Liver Cancer
by Alessandra Caligiuri, Stefano Gitto, Giulia Lori, Fabio Marra, Maurizio Parola, Stefania Cannito and Alessandra Gentilini
Cancers 2022, 14(17), 4211; https://doi.org/10.3390/cancers14174211 - 30 Aug 2022
Cited by 7 | Viewed by 2314
Abstract
Primary liver cancers represent the third-most-common cause of cancer-related mortality worldwide, with an incidence of 80–90% for hepatocellular carcinoma (HCC) and 10–15% for cholangiocarcinoma (CCA), and an increasing morbidity and mortality rate. Although HCC and CCA originate from independent cell populations (hepatocytes and [...] Read more.
Primary liver cancers represent the third-most-common cause of cancer-related mortality worldwide, with an incidence of 80–90% for hepatocellular carcinoma (HCC) and 10–15% for cholangiocarcinoma (CCA), and an increasing morbidity and mortality rate. Although HCC and CCA originate from independent cell populations (hepatocytes and biliary epithelial cells, respectively), they develop in chronically inflamed livers. Evidence obtained in the last decade has revealed a role for cytokines of the IL-6 family in the development of primary liver cancers. These cytokines operate through the receptor subunit gp130 and the downstream Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathways. Oncostatin M (OSM), a member of the IL-6 family, plays a significant role in inflammation, autoimmunity, and cancer, including liver tumors. Although, in recent years, therapeutic approaches for the treatment of HCC and CCA have been implemented, limited treatment options with marginal clinical benefits are available. We discuss how OSM-related pathways can be selectively inhibited and therapeutically exploited for the treatment of liver malignancies. Full article
(This article belongs to the Special Issue Signaling Pathways Involved in Liver Cancer Development and Progression)
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19 pages, 1238 KiB  
Review
Targeting Wnt/β-Catenin Pathways in Primary Liver Tumours: From Microenvironment Signaling to Therapeutic Agents
by Federico Selvaggi, Teresa Catalano, Roberto Cotellese and Gitana Maria Aceto
Cancers 2022, 14(8), 1912; https://doi.org/10.3390/cancers14081912 - 10 Apr 2022
Cited by 15 | Viewed by 3708
Abstract
Primary liver cancers (PLCs) are steadily increasing in incidence and mortality in the world. They have a poor prognosis due to their silent nature, late discovery and resistance to common chemotherapy. At present, there are limited treatment alternatives, and the understanding of PLC [...] Read more.
Primary liver cancers (PLCs) are steadily increasing in incidence and mortality in the world. They have a poor prognosis due to their silent nature, late discovery and resistance to common chemotherapy. At present, there are limited treatment alternatives, and the understanding of PLC molecular aspects is essential to develop more efficient drugs and therapeutic surgical and loco-regional strategies. A clear causal link with liver damage, inflammation, and regeneration has been found in the occurrence of PLC over the last few decades. Physiologically, Wingless/It (Wnt)-β-catenin signaling plays a key role in liver development, metabolic zonation and regeneration. Loss of functional homeostasis of this pathway appears to be a major driver of carcinogenesis in the liver parenchyma. In the hepatic microenvironment, molecular deregulations that exceed the Wnt signaling biological capacity can induce tumor initiation and progression. Indeed, somatic mutations are identified in key components of canonical and non-canonical Wnt signaling and in PLCs and precancerous lesions. In this review, the altered functions of Wnt/β-catenin signaling are considered in human PLCs, with emphasis on hepatocellular carcinomas (HCC), cholangiocarcinomas (CCA) and hepatoblastomas (HB). Based on recent literature, we also focused on liver cancerogenesis through Wnt deregulation. An overview of preclinical and clinical studies on approved and experimental drugs, targeting the Wnt/β-catenin cascade in PLCs, is proposed. In addition, the clinical implication of molecule inhibitors that have been shown to possess activity against the Wnt pathway in association with conventional surgical and loco-regional therapies are reviewed. Full article
(This article belongs to the Special Issue Signaling Pathways Involved in Liver Cancer Development and Progression)
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