Hypoxia‑induced SREBP1‑mediated lipogenesis and autophagy promote cell survival via fatty acid oxidation in breast cancer cells

Oncology Letters, Год журнала: 2025, Номер 29(4)

Опубликована: Фев. 7, 2025

In the hypoxic tumor microenvironment, cancer cells undergo metabolic reprogramming to survive. The present study aimed assess effects of conditions on lipid metabolism breast elucidate mechanisms by which survive in an unfavorable environment. Cell viability was assessed trypan blue staining, MTT and Annexin V‑PI assays. Intracellular levels were quantified using Nile red stain with immunofluorescence (IF). Autophagy detected LC3 antibody, Cyto‑ID stain, IF, Western blotting, flow cytometry. Fatty acid oxidation (FAO) ATP production analyzed specific assays, while gene expression reverse transcription‑polymerase chain reaction. siRNA transfection used for knockdown, Kaplan‑Meier analysis performed survival analysis. Fatostatin rapamycin served as inhibitor sterol regulatory element‑binding protein 1 (SREBP1) autophagy inducer, respectively. Under conditions, triple‑negative (TNBC) MDA‑MB‑231 showed markedly increased proliferation rates compared normal (MCF‑10A) estrogen receptor‑positive (MCF‑7), no change apoptosis. lipogenesis, FAO‑related enzymes activation SREBP1, a key transcription factor lipogenic genes, whereas these changes not observed MCF‑7 cells. When SREBP1 inhibited chemical inhibitors siRNA, lipogenic, autophagic decreased, resulting reduced cells; however, this effect restored when inducer added. demonstrated that higher patients TNBC associated worse prognosis, suggesting SREBP1‑mediated under hypoxia is essential cell survival. results indicate strategies targeting could be exploited treat improve prognosis.

Язык: Английский

---

Metabolic expression profiling analysis reveals pyruvate-mediated EPHB2 upregulation promotes lymphatic metastasis in head and neck squamous cell carcinomas

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 12, 2025

Lymphatic metastasis is a well-known factor for initiating distant of head and neck squamous cell carcinoma (HNSCC), which caused major death in most patients with cancer. Meanwhile, metabolic reprogramming to support regarded as prominent hallmark cancers. However, how disorders drive HNSCC remains unclear. We firstly established new classification based on metabolism gene expression profiles from the TCGA GEO database, identified an enriched carbohydrate subgroup was significantly associated lymphatic worse clinical outcome. Moreover, we found that highly activated pyruvate endowed tumors EPHB2 upregulation promoted tumor lymphangiogenesis independently VEGF-C/VEGFR3 signaling pathway. Mechanically, high nuclear acetyl-CoA production histone acetylation, turn transcriptionally upregulated secretion cells. bound EFNB1 endothelial cells YAP/TAZ cytoplasmic retention, alleviated YAP/TAZ-mediated prospero homeobox protein 1 (PROX1) transcriptional repression, then triggered lymphangiogenesis. Importantly, combined treatment EFNB1-Fc VEGFR3 inhibitor synergistic abrogated vitro vivo, suggesting targeting might be potential strategy no or slight response inhibitor. These findings uncover mechanism by linked provides promising therapeutic prevention metastasis.

Язык: Английский

---

Clinical significance of lipid pathway-targeted therapy in breast cancer

Frontiers in Pharmacology, Год журнала: 2025, Номер 15

Опубликована: Янв. 6, 2025

Globally, breast cancer represents the most common and primary cause of death by in women. Lipids are crucial human physiology, serving as vital energy reserves, structural elements biological membranes, essential signaling molecules. The metabolic reprogramming lipid pathways has emerged a critical factor progression, drug resistance, patient prognosis. In this study, we delve into clinical implications pathway-targeted therapy cancer. We highlight key enzymes potential therapeutic targets involved metabolism reprogramming, their associations with progression treatment outcomes. Furthermore, detail trials exploring anticancer chemopreventive activity therapies targeting these However, efficacy remains controversial, highlighting urgent need for predictive biomarkers to identify subpopulations likely benefit from such treatment. propose Selective Lipid Metabolism Therapy Benefit Hypothesis, emphasizing importance personalized medicine optimizing patients.

Язык: Английский

---

Soy Isoflavone Genistein Enhances Tamoxifen Sensitivity in Breast Cancer via microRNA and Glucose Metabolism Modulation

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(2), С. 733 - 733

Опубликована: Янв. 16, 2025

Breast cancer treatment has advanced significantly, particularly for estrogen receptor-positive (ER+) tumors. Tamoxifen, an antagonist, is widely used; however, approximately 40% of patients develop resistance. Recent studies indicate that microRNAs, especially miR-155, play a critical role in this Our analysis MCF-7 tamoxifen-sensitive (TAM-S) and tamoxifen-resistant (TAM-R) cells revealed miR-155 significantly upregulated TAM-R cells. Overexpression TAM-S increased resistance to tamoxifen. Additionally, genistein, natural isoflavone from soybeans, effectively downregulated its targets associated with apoptosis glucose metabolism, including STAT3 hexokinase 2 (HK2). Notably, genistein also decreased cell migration, suggesting potential anti-metastatic effects. Furthermore, reduced consumption, indicating overcome miR-155-mediated tamoxifen modulate the Warburg effect. These findings highlight as promising therapeutic agent overcoming ER+ breast merit further investigation.

Язык: Английский

---

Exploring the metabolic alterations in cervical cancer induced by HPV oncoproteins: From mechanisms to therapeutic targets

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2025, Номер unknown, С. 189292 - 189292

Опубликована: Март 1, 2025

The role of human Papillomavirus (HPV) in metabolic reprogramming is implicated the development and progression cervical cancer. During carcinogenesis, cancer cells modify various pathways to generate energy sustain their growth development. Cervical cancer, one most prevalent malignancies affecting women globally, involves alterations such as increased glycolysis, elevated lactate production, lipid accumulation. oncoproteins, primarily E6 E7, which are encoded by high-risk HPVs, facilitate accumulation several markers, promoting not only but also metastasis, immune evasion, therapy resistance. HPV oncoproteins interact with cellular MYC (c-MYC), retinoblastoma protein (pRB), p53, hypoxia-inducible factor 1α (HIF-1α), leading induction favour Warburg effect. Metabolic enables persist for an extended period accelerates This review summarizes contributions Additionally, this provides insights into how opens avenues novel therapeutic strategies, including discovery new repurposed drugs that could be applied treat

Язык: Английский

---

MultiOmics analysis of metabolic dysregulation and immune features in breast cancer

International Immunopharmacology, Год журнала: 2025, Номер 152, С. 114376 - 114376

Опубликована: Март 6, 2025

Язык: Английский

---

SLC7A5/E2F1/PTBP1/PKM2 axis mediates progression and therapy effect of triple-negative breast cancer through the crosstalk of amino acid metabolism and glycolysis pathway

Cancer Letters, Год журнала: 2025, Номер unknown, С. 217612 - 217612

Опубликована: Март 1, 2025

Triple-negative breast cancer (TNBC) is one of the most challenging malignancies with highest mortality rates among women. TNBC relies on both amino acid metabolism and glycolysis to fuel its bioenergetic biosynthetic demand. However, potential crosstalk between these two metabolic pathways impact progression remains largely unexplored. In this study, we observed that SLC7A5, a key transporter, was upregulated in strongly associated poor patient prognosis. We demonstrated elevated SLC7A5 expression activated pathway promoted cell proliferation, tumor growth, therapeutic resistance by inducing switch from PKM1 PKM2 expression, thereby mediating glycolysis. further identified upregulation resulted miR-152 suppression, which regulates cellular function growth. addition, miR-152/SLC7A5 axis mediated PTBP1, maintains balance PKM2, linking signaling pathway. To understand mechanism PTBP1 upregulation, E2F1 transcriptionally through direct binding at seed site, while also induced TNBC. This novel SLC7A5/ E2F1/PTBP1 plays crucial role regulating essential for effectiveness. Our findings offer valuable insights into molecular mechanisms underlying reprogramming highlight targets future interventions.

Язык: Английский

---

Editorial: Molecular mechanisms and therapeutic targets of cancer metastasis and therapy resistance

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Март 5, 2025

from the primary tumor site to distant organs, where they form secondary foci.The occurrence of metastasis involves complex cellular signaling pathways and changes in microenvironment (1). Tumor resistance, especially chemotherapy, targeted therapy, immunotherapy, significantly impacts treatment efficacy, resulting recurrence cancer progression. To improve survival quality life patients, it is urgent understand molecular mechanisms drug resistance identify new therapeutic targets.Tumor a multi-step process, involving detachment cells, invasion, dissemination through blood or lymphatic systems, growth organs. Epithelial-Mesenchymal Transition (EMT) critical process which cells acquire invasive metastatic potential (2,3). The (e.g. cancer-associated fibroblasts, etc.) immune tumor-associated macrophages, also participate (4).Additionally, angiogenesis an important condition for metastasis. Deregulation Cuproptosis has been linked metastasis, recent review by Wang et al., unbalanced levels copper promote angiogenesis, enabling cell spread (Frontiers oncology. 2023;13:1288504.). Moreover, could degrade extracellular matrix secretion metalloproteinases other enzymes, creating conditions crossing tissue barriers (5). Some molecules are involved cells. Adhesion integrins, cadherins, etc.), factors cytokines epidermal factor, platelet-derived Wnt/βcatenin pathway, PI3K/Akt/mTOR pathway play key roles (6,7). Min al. recently reviewed impact adhesion-associated molecule Desmoglein-2 (DSG2) on adhesion, migration, vasculogenic mimicry. More importantly, proposed that pro-tumorigenic anti-tumorigenic function DSG2 context dependent 2023;13:1327478.).Tumor significant challenge treatment, as employ various render drugs ineffective reduce their efficacy. P-glycoprotein, multidrug resistance-associated proteins family, breast protein examples efflux pumps expel chemotherapy (8). Gene mutations including PIK3CA, KRAS, EGFR, p53 OCT4 have related phenotype (9). undergo metabolic reprogramming increasing antioxidant enhance (10,11). DNA methylation, histone modification noncoding RNAs regulation alter gene expression leading escaping drug-induced death (12). repair capabilities resist damage induced drugs. Kaljunen found inactivation Fanconi anemia reverse prostate during DNA-damaging line-specific manner 2023;13:1260826.). apoptotic would ability lead (13). stem small population within possess self-renewal multi-lineage differentiation capabilities, (14). High heterogeneity makes vary sensitivity with some potentially harboring genetic phenotypic features (15). Immune checkpoint inhibitors PD-1/PD-L1 nivolumab, pembrolizumab, system attack tumors, intensively investigated several cancers (17). Immunotherapy targeting specific antigens (e.g., HPV vaccines) boosts memory prevent (18). Taking into consideration, combining multiple approaches (such immunotherapy chemotherapy) become strategy. target different provide comprehensive against strategy.Tumor two major challenges treatment. Currently, progress made research targets resistance. In future, further needed discover more effective develop precise, efficient, low-toxicity strategies outcomes rates patients. Combination therapies, such therapies radiotherapy, may be direction overcome deserve in-depth exploration. Additionally, continuous development technologies CRISPR editing, single-cell sequencing), we expect obtain precise strategies. By continuously delving open up avenues, improving

Язык: Английский

---

The cGAS-STING pathway in cancer immunity: dual roles, therapeutic strategies, and clinical challenges

Essays in Biochemistry, Год журнала: 2025, Номер 69(02)

Опубликована: Март 7, 2025

The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is a crucial component the host's innate immunity and plays central role in detecting cytosolic double-stranded DNA from endogenous exogenous sources. Upon activation, cGAS synthesizes cGAMP, which binds to STING, triggering cascade immune responses, including production type I interferons pro-inflammatory cytokines. In context cancers, cGAS-STING can exert dual roles: on one hand, it promotes anti-tumor by enhancing antigen presentation, stimulating T-cell inducing direct tumor cell apoptosis. On other chronic particularly tumors with chromosomal instability, lead suppression progression. Persistent signaling results up-regulation checkpoint molecules such as PD-L1, contributing evasion metastasis. Consequently, strategies targeting have consider balance activation tolerance caused activation. This review explores mechanisms underlying both protumor roles pathway, focus potential therapeutic approaches, challenges faced their clinical application, along corresponding solutions.

Язык: Английский

---

Current advancement of immune function paradox of tumour-infiltrating cells and their immunotherapeutic targets: a mini-review

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

Язык: Английский

---