Next-Cell Hypothesis: Mechanism of Obesity-Associated Carcinogenesis.


Journal

Advances in experimental medicine and biology
ISSN: 0065-2598
Titre abrégé: Adv Exp Med Biol
Pays: United States
ID NLM: 0121103

Informations de publication

Date de publication:
2024
Historique:
medline: 17 9 2024
pubmed: 17 9 2024
entrez: 17 9 2024
Statut: ppublish

Résumé

Higher body fat content is related to a higher risk of mortality, and obesity-related cancer represents approximately 40% of all cancer patients diagnosed each year. Furthermore, epigenetic mechanisms are involved in cellular metabolic memory and can determine one's predisposition to being overweight. Low-grade chronic inflammation, a well-established characteristic of obesity, is a central component of tumor development and progression. Cancer-associated adipocytes (CAA), which enhance inflammation- and metastasis-related gene sets within the cancer microenvironment, have pro-tumoral effects. Adipose tissue is a major source of the exosomal micro ribonucleic acids (miRNAs), which modulate pathways involved in the development of obesity and obesity-related comorbidities. Owing to their composition of cargo, exosomes can activate receptors at the target cell or transfer molecules to the target cells and thereby change the phenotype of these cells. Exosomes that are released into the extracellular environment are internalized with their cargo by neighboring cells. The tumor-secreted exosomes promote organ-specific metastasis of tumor cells that normally lack the capacity to metastasize to a specific organ. Therefore, the communication between neighboring cells via exosomes is defined as the "next-cell hypothesis." The reciprocal interaction between the adipocyte and tumor cell is realized through the adipocyte-derived exosomal miRNAs and tumor cell-derived oncogenic miRNAs. The cargo molecules of adipocyte-derived exosomes are important messengers for intercellular communication involved in metabolic responses and have very specific signatures that direct the metabolic activity of target cells. RNA-induced silencing regulates gene expression through various mechanisms. Destabilization of DICER enzyme, which catalyzes the conversion of primary miRNA (pri-miRNA) to precursor miRNA (pre-miRNA), is an important checkpoint in cancer development and progression. Interestingly, adipose tissue in obesity and tumors share similar pathogenic features, and the local hypoxia progress in both. While hypoxia in obesity leads to the adipocyte dysfunction and metabolic abnormalities, in obesity-related cancer cases, it is associated with worsened prognosis, increased metastatic potential, and resistance to chemotherapy. Notch-interleukin-1 (IL-1)-Leptin crosstalk outcome is referred to as "NILCO effect." In this chapter, obesity-related cancer development is discussed in the context of "next-cell hypothesis," miRNA biogenesis, and "NILCO effect."

Identifiants

pubmed: 39287871
doi: 10.1007/978-3-031-63657-8_25
doi:

Substances chimiques

MicroRNAs 0

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

727-766

Informations de copyright

© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.

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Auteurs

Ayse Basak Engin (AB)

Faculty of Pharmacy, Department of Toxicology, Gazi University, Hipodrom, Ankara, Turkey. abengin@gmail.com.

Atilla Engin (A)

Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey.
Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey.

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