The critical role of glutamine and fatty acids in the metabolic reprogramming of anoikis-resistant melanoma cells

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Авг. 8, 2024

Introduction: Circulating tumor cells (CTCs) represent the sub-population of shed into vasculature and able to survive in bloodstream, adhere target vascular endothelial cells, re-growth distant organ. CTCs have been found blood most solid tumor-bearing patients are used as a diagnostic marker. Although complex genotypic phenotypic signature characterizes CTCs, ability suspension constitutes critical property, known resistance anoikis , e.g., resist apoptosis resulting from loss substrate adhesion. Here, we selected melanoma resistant studied their metabolic reprogramming, with aim identifying new targets CTCs. Methods: Subpopulations expressing high -resistant phenotype were by three consecutive rocking exposures for characteristics. Moreover, tested efficacy different inhibitors targeting glycolysis (2DG), LDHA (LDHA-in-3), mitochondrial electron transport chain I (rotenone), glutaminase (BPTES), fatty acid transporter (SSO), synthase (denifanstat), CPT1 (etomoxir), inhibit cell survival colony formation after 24 h condition. Results: Anoikis- displayed higher grow on agarose-covered dishes respect control viability capability further step They showed also an epithelial-to-mesenchymal transition associated invasiveness stemness-like phenotype. Anoikis reprogramming characteristic glycolytic metabolism toward more oxidative based use glutamine acids, while re-adhesion reversed glycolysis. The treatment highlighted effectiveness rotenone, BPTES, SSO, etomoxir reducing capable surviving suspension, confirming dependence phosphorylation, using acids important fuels. Discussion: This finding opens up therapeutic strategies oxidation metastases.

Язык: Английский

---

Immune Cells: Critical Players in Drug Resistance

Опубликована: Янв. 1, 2024

The chapter explores the complicated relationship between immune cells and cancer drug resistance. cell composition in tumor microenvironment (TME), encompassing B cells, effector regulatory T tumor-associated macrophages (TAMs), myeloid-derived suppressor (MDSCs), neutrophils (TANs), plays a decisive role tumorigenesis. Various studies showed that MDSCs can create immunosuppressive microenvironment, allowing to evade drug-induced cytotoxicity. dynamics of influenced by play crucial modulating responsiveness. navigates through signaling pathways, molecular cross talk, adaptive mechanisms define landscape context It potential immunotherapeutic interventions, such as checkpoint inhibitors, recalibrate responses overcome resistance mechanisms. In essence, this exploration underscores pivotal shaping destiny By deciphering intricacies these interactions, aims provide insights pave way for innovative therapeutic strategies, pushing boundaries treatment toward greater efficacy resilience against

Язык: Английский

---

Autophagy regulates apoptosis of colorectal cancer cells based on signaling pathways

Discover Oncology, Год журнала: 2024, Номер 15(1)

Опубликована: Авг. 25, 2024

Colorectal cancer is a common malignant tumor of the digestive system. Its morbidity and mortality rank among highest in world. Cancer development associated with aberrant signaling pathways. Autophagy process cell self-digestion that maintains intracellular environment has bidirectional regulatory role cancer. Apoptosis one important death programs cells able to inhibit development. Studies have shown variety substances can regulate autophagy apoptosis colorectal through pathways, participate regulation on apoptosis. In this paper, we focus relevant research based involvement related pathways order provide new ideas therapeutic directions for treatment

Язык: Английский

---

The multi-omics analysis identifies a novel cuproptosis-anoikis-related gene signature in prognosis and immune infiltration characterization of lung adenocarcinoma

Heliyon, Год журнала: 2023, Номер 9(3), С. e14091 - e14091

Опубликована: Фев. 27, 2023

Lung adenocarcinoma (LUAD) has emerged as one of the most aggressive lethal cancers. Anoikis serves programmed apoptosis initiated by detachment cells from extracel-lular matrix. Cuproptosis is distinct traditional cell death modalities. The above two modes are both closely related to tumor progression, prognosis, and treatment. However, whether they have synergistic effects in LUAD deserves further investigation.The anoikis-related prognostic genes (ANRGs) co-expressed with cuproptosis-associated (CAGs) were screened using correlation analysis, analysis variance, least absolute shrinkage, selection operator (LASSO), COX regression followed functional then risk score model was constructed. Using consensus clustering, relationship between different subtypes clinicopathological features, immune infiltration characteristics, somatic mutations analyzed. A nomogram developed incorporating clinical information, which provided a prediction survival patients. Finally, comprehensive ANRGs performed verified HPA database.A total 27 associated cuproptosis obtained. On this basis, three identified, differences prognosis observed. been constructed seven signatures (EIF2AK3, IKZF3, ITGAV, OGT, PLK1, TRAF2, XRCC5). highly reliable help formulate treatment strategies based on features LUAD. seven-gene signature turned out be strongly linked validated single-cell data. Immunohistochemistry proved that all them expressed tissues.This study reveals potential cuproptosis-related microenvironment (TME), mutation can applied for predicting develop individualized strategies.

Язык: Английский

---

Roles of anoikis in hepatocellular carcinoma: mechanisms and therapeutic potential

Medical Oncology, Год журнала: 2025, Номер 42(3)

Опубликована: Янв. 30, 2025

Язык: Английский

---