ArticleProceedings of the National Academy of Sciences of the United States of America2017
Hippo pathway mediates resistance to cytotoxic drugs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 92 citations in OpenAlex.
- Hippo pathway at the crossroads of stemness and therapeutic resistance in breast cancer.Molecular oncology · 2026Review
- Deep Learning-Powered Scalable Cancer Organ Chip for Cancer Precision Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- A systems approach identifies MERTK as a therapeutic vulnerability in ZFTA-RELA-driven ependymomas.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- YAP1 Is a Crucial Nexus in the Tumor Microenvironment.Current medical science · 2026Review
- Review
- Discovery and Optimization of LATS1 and LATS2 Kinase Inhibitors for Use in Regenerative Medicine.Journal of medicinal chemistry · 2025Article
- Preventing chemotherapy-induced ovarian damage through PI3K/AKT and Hippo pathway regulation.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Review
- Regulation of Cell-Nanoparticle Interactions through Mechanobiology.Nano letters · 2025Article
- Article
- Cell-cell contacts prevent t-BuOOH-triggered ferroptosis and cellular damage in vitro by regulation of intracellular calcium.Archives of toxicology · 2024Article
- YAP inhibition overcomes adaptive resistance in HER2-positive gastric cancer treated with trastuzumab via the AKT/mTOR and ERK/mTOR axis.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2024Article
- PRMT1 promotes epigenetic reprogramming associated with acquired chemoresistance in pancreatic cancer.Cell reports · 2024Article
- Article
- Article
- Role of YAP Signaling in Regulation of Programmed Cell Death and Drug Resistance in Cancer.International journal of biological sciences · 2024Review
- Biological insights in non-small cell lung cancer.Cancer biology & medicine · 2023Review
- New insights into the ambivalent role of YAP/TAZ in human cancers.Journal of experimental & clinical cancer research : CR · 2023Review
- Spontaneously evolved progenitor niches escape Yap oncogene addiction in advanced pancreatic ductal adenocarcinomas.Nature communications · 2023Article
- Atractylodin and β-eudesmol from Atractylodes lancea (Thunb.) DC. Inhibit Cholangiocarcinoma Cell Proliferation by Downregulating the Notch Signaling Pathway.Asian Pacific journal of cancer prevention : APJCP · 2023Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Chemotherapy is widely used for cancer treatment, but its effectiveness is limited by drug resistance. Here, we report a mechanism by which cell density activates the Hippo pathway, which in turn inactivates YAP, leading to changes in the regulation of genes that control the intracellular concentrations of gemcitabine and several other US Food and Drug Administration (FDA)-approved oncology drugs. Hippo inactivation sensitizes a diverse panel of cell lines and human tumors to gemcitabine in 3D spheroid, mouse xenografts, and patient-derived xenograft models. Nuclear YAP enhances gemcitabine effectiveness by down-regulating multidrug transporters as well by converting gemcitabine to a less active form, both leading to its increased intracellular availability. Cancer cell lines carrying genetic aberrations that impair the Hippo signaling pathway showed heightened sensitivity to gemcitabine. These findings suggest that "switching off" of the Hippo-YAP pathway could help to prevent or reverse resistance to some cancer therapies.
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What OpenQuestion holds
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.