Cancer, Hypoxia, and Metabolism

Lactate cannot replace glucose for maintaining the viability of mouse and human glioma cells

This study shows lactate cannot replace glucose to maintain viability in mouse and human glioma cells, but supports lactate utilization in non-neoplastic macrophages.

Complex I Drives Glutamine-Dependent TCA Cycle to Support Viability of MYChigh Breast Cancer Cells

This study identifies enhanced mitochondrial respiration and glutamine-dependent TCA cycle as vulnerabilities in MYChigh breast cancer cells, showing synthetic lethality with complex I inhibitors.

Image-Guided Targeting of Mitochondrial Metabolism Sensitizes Pediatric Malignant Rhabdoid Tumors to Low Dose Radiotherapy

This study shows that targeting mitochondrial metabolism with Atovaquone enhances radiotherapy effectiveness in pediatric rhabdoid tumors by improving tumor oxygenation.

Creatine synthesis is a tumor suppressor pathway hypostatic to one-carbon metabolism

The paper shows MTHFD2 supports creatine synthesis in PTLD models by driving glycine production, and its loss reveals tumor-suppressive effects through metabolic epistasis.

Mechanistic studies of PFKFB2 reveals a novel inhibitor of its kinase activity

The paper identifies and validates a new inhibitor, B2, of PFKFB2 kinase activity through enzymatic assays and metabolic profiling in A-498 cells.

Lactate dehydrogenase A-coupled NAD+ regeneration is critical for acute myeloid leukemia cell survival

This study shows that LDHA is essential for maintaining NAD+/NADH balance in AML cells, and its inhibition leads to cell death, suggesting it as a therapeutic target.

Adenine nucleotide translocase 2 silencing promotes metabolic adaptations and anoikis in P19 embryonal carcinoma stem cells

This study shows that silencing ANT2 in P19 embryonal carcinoma stem cells reduces cell growth, promotes metabolic shifts, and increases anoikis sensitivity.

Serine auxotrophy is a targetable vulnerability driven by PSAT1 suppression in AML

The paper identifies serine auxotrophy in AML as a vulnerability driven by PSAT1 suppression, showing sensitivity to serine/glycine restriction and potential therapeutic targeting.

Computational modeling of cancer cell metabolism along the catabolic-anabolic axes

This paper develops a computational model of cancer metabolism integrating catabolic and anabolic pathways, identifying four metabolic phenotypes and their association with patient survival.

Cancer cells differentially modulate mitochondrial respiration to alter redox state and enable biomass synthesis in nutrient-limited environments

The paper shows cancer cells adjust mitochondrial respiration to alter NAD+/NADH ratios, enhancing biomass synthesis and proliferation under nutrient limitation.

HIF1α and HIF2α mRNA Expression in Oral Squamous Cell Carcinoma does not correlate with protein expression

This study compares HIF1α and HIF2α mRNA expression in oral squamous cell carcinoma (OSCC) tissues to adjacent normal mucosa, finding no significant difference in expression levels.

The anti-metabolite KAT/3BP has in vitro and in vivo anti-tumor activity in lymphoma models

This study evaluates KAT/3BP, a 3BP derivative, showing in vitro and in vivo anti-tumor activity against lymphoma models, including resistant cell lines and synergistic effects with existing therapies.

Erythrocytosis-inducing PHD2 mutations implicate biological role for N-terminal prolyl-hydroxylation in HIF1α oxygen-dependent degradation domain

The paper identifies PHD2 mutations that affect N-terminal prolyl-hydroxylation of HIF1α, challenging the belief that this site is dispensable for oxygen-dependent degradation.

Glutamine transporters regulate prostate cancer radiosensitivity through NUPR1-mediated stress response

This study shows that glutamine transporters regulate prostate cancer radiosensitivity via NUPR1-mediated stress response, with targeting these transporters enhancing radiosensitivity and improving treatment outcomes.

STAMBPL1 activates the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1 to promote angiogenesis in triple-negative breast cancer

This study identifies STAMBPL1's role in promoting angiogenesis in triple-negative breast cancer by activating the GRHL3/HIF1A/VEGFA axis through interaction with FOXO1.

Convergent genetic adaptation in human tumors developed under systemic hypoxia and in populations living at high altitudes

This study links EPAS1HIF2 genetic adaptations in high-altitude populations to similar mutations in hypoxia-driven tumors, showing shared mechanisms in hypoxia response and tumorigenesis.

Metabolic buffering suppresses phenotype switching in cancer

This study shows that glycogen storage and metabolic buffering suppress phenotype switching in melanoma, with low glycogen levels linked to invasion and poor survival.

Cancer Cell Adaptation to Cycling Hypoxia: Integrating Mathematical Modeling with Experimental Validation of HIF-1 Dynamics

The paper models and experimentally validates how HIF-1 dynamics in cycling hypoxia lead to specific gene expression patterns linked to cancer progression.

Hypoxia-induced extracellular matrix changes are conserved in cancer and directly impact radiotherapy benefit

The paper identifies hypoxia-induced ECM changes across cancers and shows they predict radiotherapy benefit.

HIF-1α regulates mitochondrial function in bone marrow-derived macrophages, but not in tissue-resident alveolar macrophages

The paper shows HIF-1α regulates glycolytic shifts and mitochondrial function differently in bone marrow-derived macrophages compared to tissue-resident alveolar macrophages.

Low extracellular pH protects cancer cells from ammonia toxicity.

This study shows that low extracellular pH reduces ammonia toxicity in cancer cells by mitigating its cytotoxic effects.

Global characterization of Dictyostelium discoideum gene expression changes under hypoxic conditions

This study characterizes transcriptomic and proteomic changes in Dictyostelium discoideum under hypoxic conditions, revealing extensive gene and protein expression remodeling.

Deletion of epithelial HKDC1 decelerates cellular proliferation and impairs mitochondrial function of tumorous epithelial cells thereby protecting from intestinal carcinogenesis in mice

This study shows that deleting HKDC1 in intestinal epithelial cells reduces tumor growth and protects against colorectal cancer in mice by impairing mitochondrial function and cell proliferation.

Deletion of Nrf1α promotes glutamine addiction of HepG2 cells and thus enhances its apoptosis caused by glutamine deprivation

This study shows that deleting Nrf1α in HepG2 cells increases glutamine addiction and enhances cell death when glutamine is deprived.

Redefining the role of Hypoxia-inducible factors (HIFs) in oxygen homeostasis

This paper challenges the conventional view of HIFs as mediators of hypoxic stress, proposing instead that HIFs prevent hypoxia by regulating electron transport and redefining the Warburg effect as a homeostatic response to metabolic demand.

Tumor hypoxia adaptation depends on FLAD1 mediated mitochondrial metabolic reprogramming

The paper identifies FLAD1 as a key gene for hypoxia adaptation in tumors and develops a deep learning model to predict hypoxia-dependent metabolic genes.

Exploiting De Novo Serine Synthesis as a Metabolic Vulnerability to Overcome Sunitinib Resistance in Advanced Renal Cell Carcinoma

This study identifies serine synthesis as a metabolic vulnerability in sunitinib-resistant renal cell carcinoma, showing that inhibiting key enzymes enhances drug sensitivity.

Deciphering Colorectal Cancer-Hepatocyte Interactions: A Multiomic Platform for Interrogation of Metabolic Crosstalk in the Liver-Tumor Microenvironment

This study uses multiomic analysis to investigate metabolic interactions between colorectal cancer cells and hepatocytes in liver metastasis, revealing metabolic shifts and potential therapeutic targets.

TFE3 fusions direct an oncogenic transcriptional program that drives OXPHOS and unveils vulnerabilities in translocation renal cell carcinoma

This study identifies TFE3 fusions driving OXPHOS in tRCC and reveals EGLN1 inhibition as a therapeutic target.

Hypoxia-inducible factor 1α is required to establish the larval glycolytic program in Drosophila melanogaster

This paper identifies Sima/Hif1 as a critical factor for establishing the larval glycolytic program in Drosophila, showing it works with dERR to regulate metabolism during development.