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The Interplay between Metabolism and Cancer and the Adipose Tissue Communication Signals

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 26820

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Special Issue Editors

Prof. Dr. Pietro Formisano

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Guest Editor

Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy
Interests: adipose tissue; growth factors; inflammation; insulin resistance; tumor–microenvironment interaction; tissue regeneration
Special Issues, Collections and Topics in MDPI journals

Dr. Lucia Csaderova

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Guest Editor

Department of Tumor Biology, Institue of Virology, Biomedical Research Center of the Slovak Academy of Sciences, Bratislava, Slovakia
Interests: hypoxia; cancer; pH regulation; 3D tumor models; metastasizing; adrenergic receptor signaling

Dr. Eliska Svastova

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Guest Editor

Special Issue Information

Dear Colleagues,

A growing body of evidence points out to Metabolism and Cancer as tightly inter-related events. Many topics, however, need to be included in the interplay between Metabolism and Cancer. First, environmental cues should be considered. Indeed, environmental modifications may deeply affect cancer development and progression, by either impinging on initial phases of cellular transformation or changing cell trajectories toward aggressiveness. In both cases, environmental factors modify cancer cell metabolism. On the other end, metabolic perturbations are growing causes of disease. Individuals with “common” metabolic diseases, including diabetes and obesity, have increased risk of several forms of cancer. Based on the peculiar immune-metabolic features, the adipose tissue is a prime suspect for its active part in cancer and “metabolic” comorbidities. An important challenge will be to decipher the signals of the bi-directional communication between cancer and adipose tissue, being the latter one of the main component at the cancer site.

Thus, the content of the special issue will aim to clarify the following open questions:

How macro- and micro-environmental modifications may contribute to cancer development and to adipose signals;
How cancer cell metabolism is relevant for cancer cell fate and outcome;
How cancer cells affect metabolic features of surrounding cells and overall metabolism;
How cancer cells and adipose tissue exchange information and communications.

Prof. Pietro Formisano
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

diabetes
obesity
glucose metabolism
lipid metabolism
adipose tissue
cancer progression
inflammation
adipokines
exosomes
tumor microenvironment

Published Papers (5 papers)

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Research

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18 pages, 4328 KiB

Open AccessArticle

The Impact of Human Lipoaspirate and Adipose Tissue-Derived Stem Cells Contact Culture on Breast Cancer Cells: Implications in Breast Reconstruction

by Asim Ejaz, Katherine S. Yang, Kaushik P. Venkatesh, Somaiah Chinnapaka, Lauren E. Kokai and J. Peter Rubin

Int. J. Mol. Sci. 2020, 21(23), 9171; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239171 - 01 Dec 2020

Cited by 10 | Viewed by 2576

Abstract

Background: Autologous fat transfer in the form of lipoaspirates for the reconstruction of the breast after breast cancer surgery is a commonly used procedure in plastic surgery. However, concerns regarding the oncologic risk of nutrient-rich fat tissue are widely debated. Previous studies have primarily focused on studying the interaction between adipose-derived stem cells (ASCs) and breast cancer cells. Methods: In this study, we performed a comprehensive analysis of the paracrine- and contact-based interactions between lipoaspirates, ASCs and breast cancer cell lines. An inverted flask culture method was used to study the contact-based interaction between lipoaspirates and breast cancer cells, while GFP-expressing breast cancer cell lines were generated to study the cell–cell contact interaction with ASCs. Three different human breast cancer cell lines, MCF-7, MDA-MB-231 and BT-474, were studied. We analyzed the impact of these interactions on the proliferation, cell cycle and epithelial-to-mesenchymal (EMT) transition of the breast cancer cells. Results: Our results revealed that both lipoaspirates and ASCs do not increase the proliferation rate of the breast cancer cells either through paracrine- or contact-dependent interactions. We observed that lipoaspirates selectively inhibit the proliferation of MCF-7 cells in contact co-culture, driven by the retinoblastoma (Rb) protein activity mediating cell cycle arrest. Additionally, ASCs inhibited MDA-MB-231 breast cancer cell proliferation in cell–cell contact-dependent interactions. Quantitative real-time PCR revealed no significant increase in the EMT-related genes in breast cancer cells upon co-culture with ASCs. Conclusion: In conclusion, this study provides evidence of the non-oncogenic character of lipoaspirates and supports the safety of clinical fat grafting in breast reconstruction after oncological surgical procedures. In vivo studies in appropriate animal models and long-term post-operative clinical data from patients are essential to reach the final safety recommendations. Full article

(This article belongs to the Special Issue The Interplay between Metabolism and Cancer and the Adipose Tissue Communication Signals)

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Review

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14 pages, 844 KiB

Open AccessReview

AdipoRon and Other Adiponectin Receptor Agonists as Potential Candidates in Cancer Treatments

by Ersilia Nigro, Aurora Daniele, Alessia Salzillo, Angela Ragone, Silvio Naviglio and Luigi Sapio

Int. J. Mol. Sci. 2021, 22(11), 5569; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115569 - 25 May 2021

Cited by 19 | Viewed by 3235

Abstract

The high mortality rate together with an ever-growing number of annual cases have defined neoplastic disorders as “the real 21st-century disease”. Its dubious distinction also results from conventional therapy failure, which has made cancer an orphan disease. Therefore, innovative and alternative therapeutic strategies are mandatory. The ability to leverage human naturally occurring anti-tumor defenses has always represented a fascinating perspective, and the immuno blockage approval in cancer treatment represents in timeline the latest success. As a multifunctional organ, adipose tissue releases a large amount of adipokines having both carcinogenic and antitumor properties. The negative correlation between serum levels and risk for developing malignancies, as well as the huge number of existing preclinical studies, have identified adiponectin as a potential anticancer adipokine. Nevertheless, its usage in clinical has constantly clashed with the inability to reproduce a mimic synthetic compound. Between 2011 and 2013, two distinct adiponectin receptor agonists were recognized, opening new scenarios even in cancer. Here, we review the first orally active adiponectin receptor agonists AdipoRon, from the discovery to the anticancer evidence. Including our latest findings in osteosarcoma models, we summarize AdipoRon and other existing agonists state-of-art, questioning about the feasibility assessment of this strategy in cancer treatment. Full article

(This article belongs to the Special Issue The Interplay between Metabolism and Cancer and the Adipose Tissue Communication Signals)

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21 pages, 3904 KiB

Open AccessReview

Emerging Roles for Browning of White Adipose Tissue in Prostate Cancer Malignant Behaviour

by Alejandro Álvarez-Artime, Belén García-Soler, Rosa María Sainz and Juan Carlos Mayo

Int. J. Mol. Sci. 2021, 22(11), 5560; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22115560 - 24 May 2021

Cited by 10 | Viewed by 3802

Abstract

In addition to its well-known role as an energy repository, adipose tissue is one of the largest endocrine organs in the organism due to its ability to synthesize and release different bioactive molecules. Two main types of adipose tissue have been described, namely white adipose tissue (WAT) with a classical energy storage function, and brown adipose tissue (BAT) with thermogenic activity. The prostate, an exocrine gland present in the reproductive system of most mammals, is surrounded by periprostatic adipose tissue (PPAT) that contributes to maintaining glandular homeostasis in conjunction with other cell types of the microenvironment. In pathological conditions such as the development and progression of prostate cancer, adipose tissue plays a key role through paracrine and endocrine signaling. In this context, the role of WAT has been thoroughly studied. However, the influence of BAT on prostate tumor development and progression is unclear and has received much less attention. This review tries to bring an update on the role of different factors released by WAT which may participate in the initiation, progression and metastasis, as well as to compile the available information on BAT to discuss and open a new field of knowledge about the possible protective role of BAT in prostate cancer. Full article

(This article belongs to the Special Issue The Interplay between Metabolism and Cancer and the Adipose Tissue Communication Signals)

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11 pages, 1012 KiB

Open AccessReview

Lipin-1, a Versatile Regulator of Lipid Homeostasis, Is a Potential Target for Fighting Cancer

by Laura Brohée, Julie Crémer, Alain Colige and Christophe Deroanne

Int. J. Mol. Sci. 2021, 22(9), 4419; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22094419 - 23 Apr 2021

Cited by 9 | Viewed by 4470

Abstract

The rewiring of lipid metabolism is a major adaptation observed in cancer, and it is generally associated with the increased aggressiveness of cancer cells. Targeting lipid metabolism is therefore an appealing therapeutic strategy, but it requires a better understanding of the specific roles played by the main enzymes involved in lipid biosynthesis. Lipin-1 is a central regulator of lipid homeostasis, acting either as an enzyme or as a co-regulator of transcription. In spite of its important functions it is only recently that several groups have highlighted its role in cancer. Here, we will review the most recent research describing the role of lipin-1 in tumor progression when expressed by cancer cells or cells of the tumor microenvironment. The interest of its inhibition as an adjuvant therapy to amplify the effects of anti-cancer therapies will be also illustrated. Full article

(This article belongs to the Special Issue The Interplay between Metabolism and Cancer and the Adipose Tissue Communication Signals)

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19 pages, 1396 KiB

Open AccessReview

The Regulation of Ferroptosis by Tumor Suppressor p53 and its Pathway

by Juan Liu, Cen Zhang, Jianming Wang, Wenwei Hu and Zhaohui Feng

Int. J. Mol. Sci. 2020, 21(21), 8387; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218387 - 09 Nov 2020

Cited by 127 | Viewed by 11980

Abstract

Tumor suppressor p53 plays a key role in tumor suppression. In addition to tumor suppression, p53 is also involved in many other biological and pathological processes, such as immune response, maternal reproduction, tissue ischemia/reperfusion injuries and neurodegenerative diseases. While it has been widely accepted that the role of p53 in regulation of cell cycle arrest, senescence and apoptosis contributes greatly to the function of p53 in tumor suppression, emerging evidence has implicated that p53 also exerts its tumor suppressive function through regulation of many other cellular processes, such as metabolism, anti-oxidant defense and ferroptosis. Ferroptosis is a unique iron-dependent form of programmed cell death driven by lipid peroxidation in cells. Ferroptosis has been reported to be involved in cancer, tissue ischemia/reperfusion injuries and neurodegenerative diseases. Recent studies have shown that ferroptosis can be regulated by p53 and its signaling pathway as well as tumor-associated mutant p53. Interestingly, the regulation of ferroptosis by p53 appears to be highly context-dependent. In this review, we summarize recent advances in the regulation of ferroptosis by p53 and its signaling pathway. Further elucidation of the role and molecular mechanism of p53 in ferroptosis regulation will yield new therapeutic strategies for cancer and other diseases, including neurodegenerative diseases and tissue ischemia/reperfusion injuries. Full article

(This article belongs to the Special Issue The Interplay between Metabolism and Cancer and the Adipose Tissue Communication Signals)

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