ArticleCancer research2022
Bcl-xL Enforces a Slow-Cycling State Necessary for Survival in the Nutrient-Deprived Microenvironment of Pancreatic Cancer.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 23 citations in OpenAlex.
- Morpho-crystallo-electronic Co-optimization of PtAu/GOx nanozyme for enhanced NIR-II photothermal-cascade catalytic tumor therapy.Materials today. Bio · 2026Article
- The underexplored complexity of pancreatic cancer: Early dissemination and quiescence.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- The lariat RNA debranching enzyme DBR1 enhances HIF-1 signaling and chemoresistance at the expense of lariat RNA processing.The Journal of biological chemistry · 2026Article
- Metabolic and transcriptional plasticity supports CD8Immunity · 2026Article
- The HIF-2 transcription factor mediates resistance to ferroptosis in pancreatic cancer.Molecular cell · 2026Article
- Heterocellular crosstalk and architecture of the pancreatic tumour microenvironment.Nature reviews. Cancer · 2026Review
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- PROTAC-mediated degradation of Bcl-xL potentiates target therapy in preclinical melanoma models.Journal of experimental & clinical cancer research : CR · 2026Article
- Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis.Signal transduction and targeted therapy · 2026Review
- Differential regulation of the proliferative and autophagic responses in murine and human pancreatic cancer cells.Autophagy reports · 2026Article
- BCL-XbioRxiv : the preprint server for biology · 2025Article
- Comparative Analysis of Primary and Liver Fibroblasts Reveals MET as a Potent Target in Pancreatic Cancer Metastasis.bioRxiv : the preprint server for biology · 2025Article
- Tumor nutrient stress gives rise to a drug tolerant cell state in pancreatic cancer.bioRxiv : the preprint server for biology · 2025Article
- De novo pyrimidine biosynthesis inhibition synergizes with BCL-XNature communications · 2025Article
- What's on the menu?: metabolic constraints in the pancreatic tumor microenvironment.The Journal of clinical investigation · 2025Review
- Dinaciclib Interrupts Cell Cycle and Induces Apoptosis in Oral Squamous Cell Carcinoma: Mechanistic Insights and Therapeutic Potential.International journal of molecular sciences · 2025Article
- Beyond glucose and Warburg: finding the sweet spot in cancer metabolism models.npj metabolic health and disease · 2024Review
- Modified C-type natriuretic peptide normalizes tumor vasculature, reinvigorates antitumor immunity, and improves solid tumor therapies.Science translational medicine · 2024Article
- Targeting of drug-tolerant persister cells as an approach to counter drug resistance in non-small cell lung cancer.Lung cancer (Amsterdam, Netherlands) · 2024Review
- Multiplexed Imaging Mass Cytometry Analysis Characterizes the Vascular Niche in Pancreatic Cancer.Cancer research · 2024Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
Solid tumors possess heterogeneous metabolic microenvironments where oxygen and nutrient availability are plentiful (fertile regions) or scarce (arid regions). While cancer cells residing in fertile regions proliferate rapidly, most cancer cells in vivo reside in arid regions and exhibit a slow-cycling state that renders them chemoresistant. Here, we developed an in vitro system enabling systematic comparison between these populations via transcriptome analysis, metabolomic profiling, and whole-genome CRISPR screening. Metabolic deprivation led to pronounced transcriptional and metabolic reprogramming, resulting in decreased anabolic activities and distinct vulnerabilities. Reductions in anabolic, energy-consuming activities, particularly cell proliferation, were not simply byproducts of the metabolic challenge, but rather essential adaptations. Mechanistically, Bcl-xL played a central role in the adaptation to nutrient and oxygen deprivation. In this setting, Bcl-xL protected quiescent cells from the lethal effects of cell-cycle entry in the absence of adequate nutrients. Moreover, inhibition of Bcl-xL combined with traditional chemotherapy had a synergistic antitumor effect that targeted cycling cells. Bcl-xL expression was strongly associated with poor patient survival despite being confined to the slow-cycling fraction of human pancreatic cancer cells. These findings provide a rationale for combining traditional cancer therapies that target rapidly cycling cells with those that target quiescent, chemoresistant cells associated with nutrient and oxygen deprivation. SIGNIFICANCE: The majority of pancreatic cancer cells inhabit nutrient- and oxygen-poor tumor regions and require Bcl-xL for their survival, providing a compelling antitumor metabolic strategy.
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