The Emerging Role of Tumor Microenvironmental Stimuli in Regulating Metabolic Rewiring of Liver Cancer Stem Cells.

cancer stem cells heterogeneity liver cancer metabolism plasticity tumor microenvironment

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
20 Dec 2022
Historique:
received: 22 11 2022
revised: 14 12 2022
accepted: 15 12 2022
entrez: 8 1 2023
pubmed: 9 1 2023
medline: 9 1 2023
Statut: epublish

Résumé

Primary liver cancer (PLC) is one of the most devastating cancers worldwide. Extensive phenotypical and functional heterogeneity is a cardinal hallmark of cancer, including PLC, and is related to the cancer stem cell (CSC) concept. CSCs are responsible for tumor growth, progression, relapse and resistance to conventional therapies. Metabolic reprogramming represents an emerging hallmark of cancer. Cancer cells, including CSCs, are very plastic and possess the dynamic ability to constantly shift between different metabolic states depending on various intrinsic and extrinsic stimuli, therefore amplifying the complexity of understanding tumor heterogeneity. Besides the well-known Warburg effect, several other metabolic pathways including lipids and iron metabolism are altered in PLC. An increasing number of studies supports the role of the surrounding tumor microenvironment (TME) in the metabolic control of liver CSCs. In this review, we discuss the complex metabolic rewiring affecting liver cancer cells and, in particular, liver CSCs. Moreover, we highlight the role of TME cellular and noncellular components in regulating liver CSC metabolic plasticity. Deciphering the specific mechanisms regulating liver CSC-TME metabolic interplay could be very helpful with respect to the development of more effective and innovative combinatorial therapies for PLC treatment.

Identifiants

pubmed: 36612000
pii: cancers15010005
doi: 10.3390/cancers15010005
pmc: PMC9817521
pii:
doi:

Types de publication

Journal Article Review

Langues

eng

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Auteurs

Margherita Correnti (M)

Department of Biomedical Sciences for Health, University of Milan, 20133 Milano, Italy.

Eleonora Binatti (E)

Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy.
European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, 20900 Monza, Italy.

Elena Gammella (E)

Department of Biomedical Sciences for Health, University of Milan, 20133 Milano, Italy.

Pietro Invernizzi (P)

Division of Gastroenterology, Center for Autoimmune Liver Diseases, Department of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy.
European Reference Network on Hepatological Diseases (ERN RARE-LIVER), San Gerardo Hospital, 20900 Monza, Italy.

Stefania Recalcati (S)

Department of Biomedical Sciences for Health, University of Milan, 20133 Milano, Italy.

Classifications MeSH