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Cancers
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Lipids and Small Metabolites in Cancer
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Lipids and Small Metabolites in Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Pathophysiology".

Deadline for manuscript submissions: closed (30 March 2024) | Viewed by 9562

Special Issue Editors

Dr. Zsolt Balogi

E-Mail Website
Guest Editor
Institute of Biochemistry and Medical Chemistry, Medical School, University of Pecs, Szigeti str. 12, 7624 Pecs, Hungary
Interests: cancer; trafficking; lipid
Dr. Laszlo Vigh

E-Mail Website
Guest Editor
Biological Research Center of the Hungarian Academy of Sciences, H-6726 Szeged, Hungary
Interests: heat shock proteins; stress sensing- and signaling; lipidomics; membrane fluidity and membrane homeostasis

Special Issue Information

Dear Colleagues,

Small molecule metabolites, such as amino acids, fatty acids, lipids, and numerous components of biochemical pathways, have emerged as a characteristic feature of tumor development. A wealth of omics data identified changes in the metabolome and the lipidome as a new hallmark of tumorigenesis. Understanding around pathological changes in the complex metabolome and lipidome has drastically improved. Cluster and pathway analyses of large datasets are inevitable bioinformatic tools to decode specific molecular patterns and their functions involved in the pathogenesis of tumors. The functional rewiring of disease-affected molecular cohorts can fuel complex multimodal therapeutic solutions with improved capacity to overcome resistance mechanisms.

This Special Issue, titled “Lipids and small metabolites in cancer”, welcomes all aspects of metabolome- and lipidome-related cancer research and review articles for a comprehensive view of this special topic based on omics screens, bioinformatics, targeted analyses, in vitro and in vivo experimental, or clinical results.

Dr. Zsolt Balogi
Dr. Laszlo Vigh
Guest Editors

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

  • lipid
  • small metabolites
  • cancer
  • metabolome- and lipidome-related
  • amino acids
  • fatty acids
  • numerous components of biochemical pathways

Published Papers (6 papers)

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Research

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16 pages, 3302 KiB  
Article
Metabolic Imaging Biomarkers of Response to Signaling Inhibition Therapy in Melanoma
by Pradeep Kumar Gupta, Stepan Orlovskiy, Fernando Arias-Mendoza, David S. Nelson, Aria Osborne, Stephen Pickup, Jerry D. Glickson and Kavindra Nath
Cancers 2024, 16(2), 365; https://doi.org/10.3390/cancers16020365 - 15 Jan 2024
Viewed by 1228
Abstract
Dabrafenib therapy for metastatic melanoma focuses on blocking growth-promoting signals produced by a hyperactive BRAF protein. We report the metabolic differences of four human melanoma cell lines with diverse responses to dabrafenib therapy (30 mg/kg; oral): WM3918 < WM9838BR < WM983B < DB-1. [...] Read more.
Dabrafenib therapy for metastatic melanoma focuses on blocking growth-promoting signals produced by a hyperactive BRAF protein. We report the metabolic differences of four human melanoma cell lines with diverse responses to dabrafenib therapy (30 mg/kg; oral): WM3918 < WM9838BR < WM983B < DB-1. Our goal was to determine if metabolic changes produced by the altered signaling pathway due to BRAF mutations differ in the melanoma models and whether these differences correlate with response to treatment. We assessed metabolic changes in isolated cells using high-resolution proton magnetic resonance spectroscopy (1H MRS) and supplementary biochemical assays. We also noninvasively studied mouse xenografts using proton and phosphorus (1H/31P) MRS. We found consistent changes in lactate and alanine, either in isolated cells or mouse xenografts, correlating with their relative dabrafenib responsiveness. In xenografts, we also observed that a more significant response to dabrafenib correlated with higher bioenergetics (i.e., increased βNTP/Pi). Notably, our noninvasive assessment of the metabolic status of the human melanoma xenografts by 1H/31P MRS demonstrated early metabolite changes preceding therapy response (i.e., tumor shrinkage). Therefore, this noninvasive methodology could be translated to assess in vivo predictive metabolic biomarkers of response in melanoma patients under dabrafenib and probably other signaling inhibition therapies. Full article
(This article belongs to the Special Issue Lipids and Small Metabolites in Cancer)
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20 pages, 4239 KiB  
Article
The Combined Inhibition of Autophagy and Diacylglycerol Acyltransferase-Mediated Lipid Droplet Biogenesis Induces Cancer Cell Death during Acute Amino Acid Starvation
by Maida Jusović, Pia Starič, Eva Jarc Jovičić and Toni Petan
Cancers 2023, 15(19), 4857; https://doi.org/10.3390/cancers15194857 - 05 Oct 2023
Cited by 2 | Viewed by 1152
Abstract
Lipid droplets (LDs) are dynamic organelles involved in the management of fatty acid trafficking and metabolism. Recent studies suggest that autophagy and LDs serve complementary roles in the protection against nutrient stress, but the autophagy–LD interplay in cancer cells is not well understood. [...] Read more.
Lipid droplets (LDs) are dynamic organelles involved in the management of fatty acid trafficking and metabolism. Recent studies suggest that autophagy and LDs serve complementary roles in the protection against nutrient stress, but the autophagy–LD interplay in cancer cells is not well understood. Here, we examined the relationship between autophagy and LDs in starving HeLa cervical cancer- and MDA-MB-231 breast cancer cells. We found that acute amino acid depletion induces autophagy and promotes diacylglycerol acyltransferase 1 (DGAT1)-mediated LD accumulation in HeLa cells. Inhibition of autophagy via late-stage autophagy inhibitors, or by knocking down autophagy-related 5 (ATG5), reduced LD accumulation in amino acid-starved cancer cells, suggesting that autophagy contributes to LD biogenesis. On the contrary, knockdown of adipose triglyceride lipase (ATGL) increased LD accumulation, suggesting that LD breakdown is mediated by lipolysis under these conditions. Concurrent inhibition of autophagy by silencing ATG5 and of LD biogenesis using DGAT inhibitors was effective in killing starving HeLa cells, whereas cell survival was not compromised by suppression of ATGL-mediated lipolysis. Autophagy-dependent LD biogenesis was also observed in the aggressive triple-negative MDA-MB-231 breast cancer cells deprived of amino acids, but these cells were not sensitized to starvation by the combined inhibition of LD biogenesis and autophagy. These findings reveal that while targeting autophagy-driven and DGAT-mediated LD biogenesis reduces the resilience of HeLa cervical cancer cells to amino acid deprivation, this strategy may not be successful in other cancer cell types. Full article
(This article belongs to the Special Issue Lipids and Small Metabolites in Cancer)
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13 pages, 1789 KiB  
Article
Plasma Metabolomics Predicts Chemotherapy Response in Advanced Pancreatic Cancer
by Hayato Muranaka, Andrew Hendifar, Arsen Osipov, Natalie Moshayedi, Veronica Placencio-Hickok, Nicholas Tatonetti, Aleksandr Stotland, Sarah Parker, Jennifer Van Eyk, Stephen J. Pandol, Neil A. Bhowmick and Jun Gong
Cancers 2023, 15(11), 3020; https://doi.org/10.3390/cancers15113020 - 01 Jun 2023
Cited by 3 | Viewed by 1543
Abstract
Pancreatic cancer (PC) is one of the deadliest cancers. Developing biomarkers for chemotherapeutic response prediction is crucial for improving the dismal prognosis of advanced-PC patients (pts). To evaluate the potential of plasma metabolites as predictors of the response to chemotherapy for PC patients, [...] Read more.
Pancreatic cancer (PC) is one of the deadliest cancers. Developing biomarkers for chemotherapeutic response prediction is crucial for improving the dismal prognosis of advanced-PC patients (pts). To evaluate the potential of plasma metabolites as predictors of the response to chemotherapy for PC patients, we analyzed plasma metabolites using high-performance liquid chromatography–mass spectrometry from 31 cachectic, advanced-PC subjects enrolled into the PANCAX-1 (NCT02400398) prospective trial to receive a jejunal tube peptide-based diet for 12 weeks and who were planned for palliative chemotherapy. Overall, there were statistically significant differences in the levels of intermediates of multiple metabolic pathways in pts with a partial response (PR)/stable disease (SD) vs. progressive disease (PD) to chemotherapy. When stratified by the chemotherapy regimen, PD after 5-fluorouracil-based chemotherapy (e.g., FOLFIRINOX) was associated with decreased levels of amino acids (AAs). For gemcitabine-based chemotherapy (e.g., gemcitabine/nab-paclitaxel), PD was associated with increased levels of intermediates of glycolysis, the TCA cycle, nucleoside synthesis, and bile acid metabolism. These results demonstrate the feasibility of plasma metabolomics in a prospective cohort of advanced-PC patients for assessing the effect of enteral feeding as their primary source of nutrition. Metabolic signatures unique to FOLFIRINOX or gemcitabine/nab-paclitaxel may be predictive of a patient’s response and warrant further study. Full article
(This article belongs to the Special Issue Lipids and Small Metabolites in Cancer)
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Review

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17 pages, 1610 KiB  
Review
Emerging Lipid Targets in Glioblastoma
by Ammar Darwish, Milán Pammer, Ferenc Gallyas, Jr., László Vígh, Zsolt Balogi and Kata Juhász
Cancers 2024, 16(2), 397; https://doi.org/10.3390/cancers16020397 - 17 Jan 2024
Viewed by 1319
Abstract
GBM accounts for most of the fatal brain cancer cases, making it one of the deadliest tumor types. GBM is characterized by severe progression and poor prognosis with a short survival upon conventional chemo- and radiotherapy. In order to improve therapeutic efficiency, considerable [...] Read more.
GBM accounts for most of the fatal brain cancer cases, making it one of the deadliest tumor types. GBM is characterized by severe progression and poor prognosis with a short survival upon conventional chemo- and radiotherapy. In order to improve therapeutic efficiency, considerable efforts have been made to target various features of GBM. One of the targetable features of GBM is the rewired lipid metabolism that contributes to the tumor’s aggressive growth and penetration into the surrounding brain tissue. Lipid reprogramming allows GBM to acquire survival, proliferation, and invasion benefits as well as supportive modulation of the tumor microenvironment. Several attempts have been made to find novel therapeutic approaches by exploiting the lipid metabolic reprogramming in GBM. In recent studies, various components of de novo lipogenesis, fatty acid oxidation, lipid uptake, and prostaglandin synthesis have been considered promising targets in GBM. Emerging data also suggest a significant role hence therapeutic potential of the endocannabinoid metabolic pathway in GBM. Here we review the lipid-related GBM characteristics in detail and highlight specific targets with their potential therapeutic use in novel antitumor approaches. Full article
(This article belongs to the Special Issue Lipids and Small Metabolites in Cancer)
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16 pages, 1181 KiB  
Review
Metabolomic-Based Approaches for Endometrial Cancer Diagnosis and Prognosis: A Review
by Manel Albertí-Valls, Cristina Megino-Luque, Anna Macià, Sònia Gatius, Xavier Matias-Guiu and Núria Eritja
Cancers 2024, 16(1), 185; https://doi.org/10.3390/cancers16010185 - 29 Dec 2023
Viewed by 916
Abstract
Endometrial cancer, the most prevalent gynecological malignancy in developed countries, is experiencing a sustained rise in both its incidence and mortality rates, primarily attributed to extended life expectancy and lifestyle factors. Currently, the absence of precise diagnostic tools hampers the effective management of [...] Read more.
Endometrial cancer, the most prevalent gynecological malignancy in developed countries, is experiencing a sustained rise in both its incidence and mortality rates, primarily attributed to extended life expectancy and lifestyle factors. Currently, the absence of precise diagnostic tools hampers the effective management of the expanding population of women at risk of developing this disease. Furthermore, patients diagnosed with endometrial cancer require precise risk stratification to align with optimal treatment planning. Metabolomics technology offers a unique insight into the molecular landscape of endometrial cancer, providing a promising approach to address these unmet needs. This comprehensive literature review initiates with an overview of metabolomic technologies and their intrinsic workflow components, aiming to establish a fundamental understanding for the readers. Subsequently, a detailed exploration of the existing body of research is undertaken with the objective of identifying metabolite biomarkers capable of enhancing current strategies for endometrial cancer diagnosis, prognosis, and recurrence monitoring. Metabolomics holds vast potential to revolutionize the management of endometrial cancer by providing accuracy and valuable insights into crucial aspects. Full article
(This article belongs to the Special Issue Lipids and Small Metabolites in Cancer)
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37 pages, 4133 KiB  
Review
Biosynthesis and Significance of Fatty Acids, Glycerophospholipids, and Triacylglycerol in the Processes of Glioblastoma Tumorigenesis
by Jan Korbecki, Mateusz Bosiacki, Izabela Gutowska, Dariusz Chlubek and Irena Baranowska-Bosiacka
Cancers 2023, 15(7), 2183; https://doi.org/10.3390/cancers15072183 - 06 Apr 2023
Cited by 4 | Viewed by 2592
Abstract
One area of glioblastoma research is the metabolism of tumor cells and detecting differences between tumor and healthy brain tissue metabolism. Here, we review differences in fatty acid metabolism, with a particular focus on the biosynthesis of saturated fatty acids (SFA), monounsaturated fatty [...] Read more.
One area of glioblastoma research is the metabolism of tumor cells and detecting differences between tumor and healthy brain tissue metabolism. Here, we review differences in fatty acid metabolism, with a particular focus on the biosynthesis of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) by fatty acid synthase (FASN), elongases, and desaturases. We also describe the significance of individual fatty acids in glioblastoma tumorigenesis, as well as the importance of glycerophospholipid and triacylglycerol synthesis in this process. Specifically, we show the significance and function of various isoforms of glycerol-3-phosphate acyltransferases (GPAT), 1-acylglycerol-3-phosphate O-acyltransferases (AGPAT), lipins, as well as enzymes involved in the synthesis of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and cardiolipin (CL). This review also highlights the involvement of diacylglycerol O-acyltransferase (DGAT) in triacylglycerol biosynthesis. Due to significant gaps in knowledge, the GEPIA database was utilized to demonstrate the significance of individual enzymes in glioblastoma tumorigenesis. Finally, we also describe the significance of lipid droplets in glioblastoma and the impact of fatty acid synthesis, particularly docosahexaenoic acid (DHA), on cell membrane fluidity and signal transduction from the epidermal growth factor receptor (EGFR). Full article
(This article belongs to the Special Issue Lipids and Small Metabolites in Cancer)
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