ArticleCancer research communications2024
Drug-resilient Cancer Cell Phenotype Is Acquired via Polyploidization Associated with Early Stress Response Coupled to HIF2α Transcriptional Regulation.
Article in Cancer research communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Tetraploids or polyploid giants: who is truly dangerous?Trends in cell biology · 2026Review
- Polyploid cancer cells surviving cisplatin reallocate central carbon sources to fuel antioxidant metabolism for survival.Molecular metabolism · 2026Article
- Aberrant polyploidization pathways in megakaryocytes as therapeutic targets in leukemia.Annals of medicine and surgery (2012) · 2026Review
- Distinct p21 dynamics drive alternative routes to whole-genome duplication through a common CDK4/6-dependent polyploid G0 state.bioRxiv : the preprint server for biology · 2026Article
- Cancer cells surviving cisplatin chemotherapy increase stress-induced OMA1 activity and mitochondrial fragmentation.Scientific reports · 2026Article
- Life history enlightened therapies: cell cycle mapping to identify molecular targets to prevent hepatocellular carcinoma.Evolution, medicine, and public health · 2026Article
- Temporal myc dynamics permit mitotic bypass, promoting polyploid phenotypes.Cancer letters · 2025Review
- Article
- Regulation of volume-regulated anion channels alters sensitivity to platinum chemotherapy.Science advances · 2024Article
- Investigating the biology of microRNA links to ALDH1A1 reveals candidates for preclinical testing in acute myeloid leukemia.International journal of oncology · 2024Review
- Polyploid cancer cells reveal signatures of chemotherapy resistance.bioRxiv : the preprint server for biology · 2024Article
- Divergent Processing of Cell Stress Signals as the Basis of Cancer Progression: Licensing NFκB on Chromatin.International journal of molecular sciences · 2024Review
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Authors and funding
22 authors at 4 institutions in 4 countries.
Funding
Abstract
Therapeutic resistance and recurrence remain core challenges in cancer therapy. How therapy resistance arises is currently not fully understood with tumors surviving via multiple alternative routes. Here, we demonstrate that a subset of cancer cells survives therapeutic stress by entering a transient state characterized by whole-genome doubling. At the onset of the polyploidization program, we identified an upregulation of key transcriptional regulators, including the early stress-response protein AP-1 and normoxic stabilization of HIF2α. We found altered chromatin accessibility, ablated expression of retinoblastoma protein (RB1), and enrichment of AP-1 motif accessibility. We demonstrate that AP-1 and HIF2α regulate a therapy resilient and survivor phenotype in cancer cells. Consistent with this, genetic or pharmacologic targeting of AP-1 and HIF2α reduced the number of surviving cells following chemotherapy treatment. The role of AP-1 and HIF2α in stress response by polyploidy suggests a novel avenue for tackling chemotherapy-induced resistance in cancer. SIGNIFICANCE: In response to cisplatin treatment, some surviving cancer cells undergo whole-genome duplications without mitosis, which represents a mechanism of drug resistance. This study presents mechanistic data to implicate AP-1 and HIF2α signaling in the formation of this surviving cell phenotype. The results open a new avenue for targeting drug-resistant cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.