Host-derived lipid transfer and metabolic reprogramming in a ciliate–algal symbiosis

BackgroundEndometrial cancer is one of the major gynecological cancers, with increasing incidence and mortality in the past decades. Emerging preclinical and clinical data have indicated its close association with obesity and dyslipidemia. Metabolism reprogramming has been considered as the hallmark of cancer, to satisfy the extensive need of nutrients and energy for survival and growth. Particularly, lipid metabolism reprogramming has aroused the researchers’ interest in the field of cancer, including tumorigenesis, invasiveness, metastasis, therapeutic resistance and immunity modulation, etc. But the roles of lipid metabolism reprogramming in endometrial cancer have not been fully understood. This review has summarized how lipid metabolism reprogramming induces oncogenesis and progression of endometrial cancer, including the biological functions of aberrant lipid metabolism pathway and altered transcription regulation of lipid metabolism pathway. Besides, we proposed novel therapeutic strategies of targeting lipid metabolism pathway and concentrated on its potential of sensitizing immunotherapy and hormonal therapy, to further optimize the existing treatment modalities of patients with advanced/metastatic endometrial cancer. Moreover, we expect that targeting lipid metabolism plus hormone therapy may block the endometrial malignant transformation and enrich the preventative approaches of endometrial cancer.ConclusionLipid metabolism reprogramming plays an important role in tumor initiation and cancer progression of endometrial cancer. Targeting the core enzymes and transcriptional factors of lipid metabolism pathway alone or in combination with immunotherapy/hormone treatment is expected to decrease the tumor burden and provide promising treatment opportunity for patients with advanced/metastatic endometrial cancer.

The deposition of Schistosoma japonicum (S. japonicum) eggs commonly induces inflammation, fibrosis, hyperplasia, ulceration, and polyposis in the colon, which poses a serious threat to human health. However, the underlying mechanism is largely neglected. Recently, the disorder of glucose and lipid metabolism was reported to participate in the liver fibrosis induced by the parasite, which provides a novel clue for studying the underlying mechanism of the intestinal pathology of the disease. This study focused on the metabolic reprogramming profiles of glucose and lipid in the colon of mice infected by S. japonicum. We found that S. japonicum infection shortened the colonic length, impaired intestinal integrity, induced egg-granuloma formation, and increased colonic inflammation. The expression of key enzymes involved in the pathways regulating glucose and lipid metabolism was upregulated in the colon of infected mice. Conversely, phosphatase and tensin homolog deleted on chromosome ten (PTEN) and its downstream signaling targets were significantly inhibited after infection. In line with these results, in vitro stimulation with soluble egg antigens (SEA) downregulated the expression of PTEN in CT-26 cells and induced metabolic alterations similar to that observed under in vivo results. Moreover, PTEN over-expression prevented the reprogramming of glucose and lipid metabolism induced by SEA in CT-26 cells. Overall, the present study showed that S. japonicum infection induces the reprogramming of glucose and lipid metabolism in the colon of mice, and PTEN may play a vital role in mediating this metabolic reprogramming. These findings provide a novel insight into the pathogenicity of S. japonicum in hosts.

The hallmark feature of metabolic reprogramming is now considered to be widespread in many malignancies, including colorectal cancer (CRC). Of the gastrointestinal tumors, CRC is one of the most common with a high metastasis rate and long insidious period. The incidence and mortality of CRC has increased in recent years. Metabolic reprogramming also has a significant role in the development and progression of CRC, especially lipid metabolic reprogramming. Many studies have reported that lipid metabolism reprogramming is similar to the Warburg effect with typical features affecting tumor biology including proliferation, migration, local invasion, apoptosis, and other biological behaviors of cancer cells. Therefore, studying the role of lipid metabolism in the occurrence and development of CRC will increase our understanding of its pathogenesis, invasion, metastasis, and other processes and provide new directions for the treatment of CRC. In this paper, we mainly describe the molecular mechanism of lipid metabolism reprogramming and its important role in the occurrence and development of CRC. In addition, to provide reference for subsequent research and clinical diagnosis and treatment we also review the treatments of CRC that target lipid metabolism.

Simple SummaryOne of the causes of failure of anticancer therapies is the reprogramming of lipid metabolism. Cells of innate and adaptive immunity present in the tumor microenvironment can be affected by this metabolic switch and thus present changes in their anti- or protumor phenotype. In this review, modifications induced by lipid metabolism will be described for innate immune cells, such as macrophages, dendritic cells and MDSCs, and also for adaptive immune cells, such as CD4+ and CD8+ T cells and B cells. Finally, antitumor therapeutic strategies targeting lipid metabolism will be presented.Over the past decade, metabolic reprogramming has been defined as a hallmark of cancer. More recently, a large number of studies have demonstrated that metabolic reprogramming can modulate the differentiation and functions of immune cells, and thus modify the antitumor response. Increasing evidence suggests that modified energy metabolism could be responsible for the failure of antitumor immunity. Indeed, tumor-infiltrating immune cells play a key role in cancer, and metabolic switching in these cells has been shown to help determine their phenotype: tumor suppressive or immune suppressive. Recent studies in the field of immunometabolism focus on metabolic reprogramming in the tumor microenvironment (TME) by targeting innate and adaptive immune cells and their associated anti- or protumor phenotypes. In this review, we discuss the lipid metabolism of immune cells in the TME as well as the effects of lipids; finally, we expose the link between therapies and lipid metabolism.

Targeting lipid metabolism via nanomedicine: A prospective strategy for cancer therapy.

Metabolic reprogramming of tumor cells is an important feature of oncogenesis and progression, with lipid metabolism playing a key role in this process. The enzymes encoded by the ACSM (Acyl-CoA Synthetase Medium-Chain Family) genes play a crucial role in fatty acid activation, affecting the energy supply and membrane synthesis of tumor cells. In recent years, research on the expression patterns of ACSM family genes in different tumor types and their regulatory mechanisms has gradually increased, revealing their close relationship with tumor development. However, current research on ACSM family genes still has some shortcomings, such as a lack of systematic large-scale clinical data support and an in-depth understanding of their regulatory networks. This work summarizes the role of ACSMs in tumor lipid metabolic reprogramming and explores their research progress as potential therapeutic targets, providing new ideas for future tumor treatment.

Objectives: The reprogramming of lipid metabolism is a new trait of cancers. However, the role of lipid metabolism in the tumor immune microenvironment (TIME) and the prognosis of gastric cancer remains unclear. Methods: Consensus clustering was applied to identify novel subgroups. ESTIMATE, TIMER, and MCPcounter algorithms were used to determine the TIME of the subgroups. The underlying mechanisms were elucidated using functional analysis. The prognostic model was established using the LASSO algorithm and multivariate Cox regression analysis. Results: Three molecular subgroups with significantly different survival were identified. The subgroup with relatively low lipid metabolic expression had a lower immune score and immune cells. The differentially expressed genes (DEGs) were concentrated in immune biological processes and cell migration via GO and KEGG analyses. GSEA analysis showed that the subgroups were mainly enriched in arachidonic acid metabolism. Gastric cancer survival can be predicted using risk models based on lipid metabolism genes. Conclusions: The TIME of gastric cancer patients is related to the expression of lipid metabolism genes and could be used to predict cancer prognosis accurately.

ObjectiveTo systematically characterize the global research landscape of metabolism-related intraocular malignancies and to validate the robustness of findings through a multi-database comparative approach.MethodsPublications from January 1, 1990, to July 31, 2025, were retrieved from the Web of Science Core Collection (WoSCC). To ensure the stability and generalizability of results, equivalent searches were performed in Scopus and PubMed, applying the same keyword set, time frame, and eligibility criteria. Bibliometric analyses were conducted using VOSviewer, CiteSpace, and GraphPad Prism to evaluate publication trends, geographic and institutional contributions, journal and author influence, keyword co-occurrence, co-citation patterns, and emerging research fronts. Cross-database validation assessed concordance in temporal trends, thematic focuses, and country rankings.ResultsA total of 1,745 WoSCC publications were included, authored by researchers from 69 countries. Global output has increased markedly since 2010, peaking in 2021. Uveal melanoma consistently emerged as the dominant intraocular tumor type in metabolic research. Major thematic clusters encompassed oxidative stress, apoptosis, hypoxia, lipid metabolism, and metabolic reprogramming, with recent shifts toward long noncoding RNA, immune infiltration, and metabolomics, signaling a transition to precision oncology. Importantly, multi-database validation demonstrated high concordance in annual publication trends, as well as strong overlap in top keywords and stability in geographical and disease foci.ConclusionThis study provides a multi-database bibliometric assessment of metabolism-related intraocular malignancy research, with offering a reliable foundation for guiding future basic and translational research in ocular oncology.

As one of novel hallmarks of cancer, lipid metabolic reprogramming has recently been becoming fascinating and widely studied. Lipid metabolic reprogramming in cancer is shown to support carcinogenesis, progression, distal metastasis, and chemotherapy resistance by generating ATP, biosynthesizing macromolecules, and maintaining appropriate redox status. Notably, increasing evidence confirms that lipid metabolic reprogramming is under the control of dysregulated non-coding RNAs in cancer, especially lncRNAs and circRNAs. This review highlights the present research findings on the aberrantly expressed lncRNAs and circRNAs involved in the lipid metabolic reprogramming of cancer. Emphasis is placed on their regulatory targets in lipid metabolic reprogramming and associated mechanisms, including the clinical relevance in cancer through lipid metabolism modulation. Such insights will be pivotal in identifying new theranostic targets and treatment strategies for cancer patients afflicted with lipid metabolic reprogramming.

Metabolic competition is a zero‐sum game between bacterial biofilms and host immune responses on the surface of medical implants. In an in vitro biofilm‐macrophages co‐culture system, it is found that suppressed lipid metabolic processes in host macrophages in the biofilm microenvironment correlates with immune tolerance and intracellular persistence. Reactivation of immune cells against bacterial infection by reprogramming lipid metabolism through the supply of lipids such as oleic acid (OA) is a promising strategy, but this cannot completely destroy the bacterial biofilms. Nanomaterial‐based zinc ion interference therapy in antibacterial field emerges relying on the outstanding benefits of nanomaterials. Therefore, a targeted nano‐fat HSA‐IR820@OA@ZIF‐8 (HIROZ) with near infrared‐II (NIR‐II) photothermal capacities is developed for the destrcution of the biofilms via zinc ion combined photothermal therapy. The improved cellular compatibility and enhanced intracellular uptake make HIROZ induce intracellular lipid droplets (LDs) formation in macrophages. Photothermal combined zinc ion‐induced metabolic interference augments the antimicrobial effect of LDs and activates lipometabolic reprogramming‐mediated antibacterial immune responses via mitochondrial stress. In the mouse wound biofilm infections model and subcutaneous implant‐associated biofilm infections (IABIs) model, HIROZ demonstrates sustained and thorough biofilm scavenging based on reprogramming of lipid metabolism, providing a new idea for metabolic interference‐centered therapeutic strategies for full‐scale IABIs eliminations.

Lipid metabolic reprogramming and associated ferroptosis in osteosarcoma: From molecular mechanisms to potential targets.

In recent years, the relationship between lipid metabolism and tumour immunotherapy has been thoroughly investigated. An increasing number of studies have shown that abnormal gene expression and ectopic levels of metabolites related to fatty acid synthesis or fatty acid oxidation affect tumour metastasis, recurrence, and drug resistance. Tumour immunotherapy that aims to promote an antitumour immune response has greatly improved the outcomes for tumour patients. However, lipid metabolism reprogramming in tumour cells or tumour microenvironment-infiltrating immune cells can influence the antitumour response of immune cells and induce tumor cell immune evasion. The recent increase in the prevalence of obesity-related cancers has drawn attention to the fact that obesity increases fatty acid oxidation in cancer cells and suppresses the activation of immune cells, thereby weakening antitumour immunity. This article reviews the changes in lipid metabolism in cells in the tumour microenvironment and describes the relationship between lipid metabolism reprogramming in multiple cell types and tumour immunotherapy.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression, which limits the availability of targeted therapies and results in poor prognosis. Immune checkpoint blockade (ICB) therapies have emerged as promising treatments by enhancing anti-tumor immunity; however, a substantial proportion of patients with TNBC exhibit primary or acquired resistance. This resistance is largely influenced by the tumor microenvironment (TME). This study uses integrated single-cell and spatial transcriptomics to elucidate key cellular mechanisms of resistance, with particular emphasis on lipid-mediated stromal-immune interactions within the TNBC TME. This investigation encompassed analysis of single-cell RNA sequencing (scRNA-seq) data from three TNBC datasets and spatial transcriptomic data from 43 TNBC samples. Spatial niches and cell-cell interactions were identified using the Multimodal Intersection Analysis (MIA) algorithm. Experimentally, adipose-derived mesenchymal stem cells (AD-SCs) were co-cultured with MDA-MB-231 TNBC cells to generate lipid-processing CAFs (lpCAFs) and subsequently co-cultured with THP-1 macrophages. Lipid metabolism and M2 polarization of macrophages were assessed using BODIPY staining, Oil Red O, qPCR, flow cytometry and Western blotting techniques. ABCA8+ lpCAFs and APOE+ lipid-associated macrophages (LAMs) exhibited significant enrichment in ICB-resistant TNBC, with co-localization at the immune-stromal junction. lpCAFs facilitated M2 macrophage polarization through lipid metabolism reprogramming, establishing an immunosuppressive TME. High ABCA8 expression demonstrated correlation with enhanced M2 macrophage infiltration, decreased cytotoxic immune cells, and poorer prognosis. Experimental validation demonstrated that lpCAFs increased expression of lipid metabolism and M2 polarization marker in macrophages, substantiating their immunosuppressive function. ABCA8+ lpCAFs and APOE+ LAMs contribute to ICB resistance in TNBC through the establishment of an immunosuppressive TME via lipid metabolism reprogramming. Therapeutic intervention targeting the ABCA8-lipid axis presents a promising strategy to enhance ICB efficacy, potentially advancing TNBC treatment outcomes and improving patient survival.

Simple SummaryCancer cells exhibit unrestrained cell growth and proliferation owing to tumor-specific characteristics such as altered metabolism. Tumor cells vary metabolic pathways to meet their needs for rapid cell growth. In this review, we focus particularly on lipid metabolism in embryonal tumors with deregulated MYCN function, specifically neuroblastoma, retinoblastoma, Wilms tumor, medulloblastoma, and rhabdomyosarcoma. We also discuss whether we can target lipid metabolism to restrict tumor cell growth and proliferation.Tumor cells reprogram their metabolism, including glucose, glutamine, nucleotide, lipid, and amino acids to meet their enhanced energy demands, redox balance, and requirement of biosynthetic substrates for uncontrolled cell proliferation. Altered lipid metabolism in cancer provides lipids for rapid membrane biogenesis, generates the energy required for unrestricted cell proliferation, and some of the lipids act as signaling pathway mediators. In this review, we focus on the role of lipid metabolism in embryonal neoplasms with MYCN dysregulation. We specifically review lipid metabolic reactions in neuroblastoma, retinoblastoma, medulloblastoma, Wilms tumor, and rhabdomyosarcoma and the possibility of targeting lipid metabolism. Additionally, the regulation of lipid metabolism by the MYCN oncogene is discussed.

NOTCH3 is increasingly implicated for its oncogenic role in many malignancies, including meningiomas. While prior work has linked NOTCH3 expression to higher-grade meningiomas and radiation therapy resistance, the metabolic phenotype of NOTCH3 activation remains unexplored in meningioma. This study demonstrates that NOTCH3 in meningiomas mediates a metabolic shift toward fatty acid oxidation (FAO), depleting lipid availability and conferring resistance to ferroptosis. Single-cell RNA sequencing of NOTCH3⁺ human meningioma cells (14,080 cells from 22 meningiomas) reveals a correlation with CD36, a membrane-bound fatty acid transporter that facilitates fatty acid uptake and directs them toward FAO. Patient-derived primary meningioma cells stratified by NOTCH3 and CD36 expression demonstrated increased maximal mitochondrial respiration in the presence of palmitate, suggesting functional upregulation of lipid metabolism in NOTCH3-expressing meningioma cells. Using the CH157-MN meningioma model, this study shows a shift in lipid catabolism with NOTCH3 intracellular domain (ICD) overexpression (CH157-MNNOTCH3 ICD) compared with empty vector controls (CH157-MNEV). Untargeted metabolomic profiling of CH157-MNNOTCH3 ICD cells revealed decreased fatty acyl-carnitine species relative to CH157-MNEV controls. Bulk RNA sequencing demonstrated upregulation of canonical FAO genes and downregulation of fatty acid synthesis genes, confirming enhancement of lipid metabolism with NOTCH3 overexpression. Targeted fatty acid analysis revealed depletion of intracellular fatty acids in CH157-MNNOTCH3 ICD cells. Functional extracellular flux assays confirmed elevated oxidative respiration in the presence of palmitate, indicating increased mitochondrial oxidative capacity. Finally, CH157-MNNOTCH3 ICD cells exhibited increased resistance to RSL3-induced ferroptosis, a phenotype reversed with CPT1 inhibition. These data establish a link between NOTCH3 signaling, lipid metabolic reprogramming, and ferroptosis evasion in aggressive meningioma cells. This metabolic shift may contribute to the malignant behavior observed in NOTCH3-expressing meningiomas, offering new insight into the biochemical vulnerabilities of these tumors.