ArticleCancer research2011
Spatial regulation of RhoA activity during pancreatic cancer cell invasion driven by mutant p53.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 166 citations in OpenAlex.
- RHOV couples EMT-associated plasticity to cytoskeletal execution of invasion and metastasis.Cell death discovery · 2026Article
- Mutant p53 regulates cancer cell invasion in complex three-dimensional environments through mevalonate pathway-dependent Rho/ROCK signaling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Duality of Collagens in Metastases of Solid Tumors.International journal of molecular sciences · 2025Review
- Polybromo 1/vimentin axis dictates tumor grade, epithelial-mesenchymal transition, and metastasis in pancreatic cancer.The Journal of clinical investigation · 2025Article
- From regulation to deregulation of p53 in hematologic malignancies: implications for diagnosis, prognosis and therapy.Biomarker research · 2024Review
- Compression-dependent microtubule reinforcement enables cells to navigate confined environments.Nature cell biology · 2024Article
- CD73 controls Myosin II-driven invasion, metastasis, and immunosuppression in amoeboid pancreatic cancer cells.Science advances · 2023Article
- Khasianine Affects the Expression of Sugar-Sensitive Proteins in Pancreatic Cancer Cells, Which Are Altered in Data from the Rat Model and Patients.ACS pharmacology & translational science · 2023Article
- Focal adhesion kinase priming in pancreatic cancer, altering biomechanics to improve chemotherapy.Biochemical Society transactions · 2022Article
- The Hippo pathway in cancer: YAP/TAZ and TEAD as therapeutic targets in cancer.Clinical science (London, England : 1979) · 2022Review
- Dynamic Stromal Alterations Influence Tumor-Stroma Crosstalk to Promote Pancreatic Cancer and Treatment Resistance.Cancers · 2021Review
- Luminescence lifetime imaging of three-dimensional biological objects.Journal of cell science · 2021Article
- Lung cancer and epithelial-mesenchymal transition.General thoracic and cardiovascular surgery · 2021Review
- Stabilized epithelial phenotype of cancer cells in primary tumors leads to increased colonization of liver metastasis in pancreatic cancer.Cell reports · 2021Article
- Time-Resolved Fluorescence Anisotropy and Molecular Dynamics Analysis of a Novel GFP Homo-FRET Dimer.Biophysical journal · 2021Article
- Acute compressive stress activates RHO/ROCK-mediated cellular processes.Small GTPases · 2020Article
- Shedding new light on RhoA signalling as a drug targetSmall GTPases · 2020Article
- Experimental pathology by intravital microscopy and genetically encoded fluorescent biosensors.Pathology international · 2020Review
- Fluorescence lifetime imaging microscopy: fundamentals and advances in instrumentation, analysis, and applications.Journal of biomedical optics · 2020Review
- Frontiers in Intravital Multiphoton Microscopy of Cancer.Cancer reports (Hoboken, N.J.) · 2020Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The ability to observe changes in molecular behavior during cancer cell invasion in vivo remains a major challenge to our understanding of the metastatic process. Here, we demonstrate for the first time, an analysis of RhoA activity at a subcellular level using FLIM-FRET (fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer) imaging in a live animal model of pancreatic cancer. In invasive mouse pancreatic ductal adenocarcinoma (PDAC) cells driven by mutant p53 (p53(R172H)), we observed a discrete fraction of high RhoA activity at both the leading edge and rear of cells in vivo which was absent in two-dimensional in vitro cultures. Notably, this pool of active RhoA was absent in noninvasive p53(fl) knockout PDAC cells, correlating with their poor invasive potential in vivo. We used dasatanib, a clinically approved anti-invasive agent that is active in this model, to illustrate the functional importance of spatially regulated RhoA. Dasatanib inhibited the activity of RhoA at the poles of p53(R172H) cells in vivo and this effect was independent of basal RhoA activity within the cell body. Taken together, quantitative in vivo fluorescence lifetime imaging illustrated that RhoA is not only necessary for invasion, but also that subcellular spatial regulation of RhoA activity, as opposed to its global activity, is likely to govern invasion efficiency in vivo. Our findings reveal the utility of FLIM-FRET in analyzing dynamic biomarkers during drug treatment in living animals, and they also show how discrete intracellular molecular pools might be differentially manipulated by future anti-invasive therapies.
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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.