AI Article Synopsis
Article Abstract
Hybrid epithelial/mesenchymal cells (E/M) are key players in aggressive cancer metastasis. It remains a challenge to understand how these cell states, which are mostly non-existent in healthy tissue, become stable phenotypes participating in collective cancer migration. The transcription factor Nrf2, which is associated with tumor progression and resistance to therapy, appears to be central to this process. Here, using a combination of immunocytochemistry, single cell biosensors, and computational modeling, we show that Nrf2 functions as a phenotypic stability factor for hybrid E/M cells by inhibiting a complete epithelial-mesenchymal transition (EMT) during collective cancer migration. We also demonstrate that Nrf2 and EMT signaling are spatially coordinated near the leading edge. In particular, computational analysis of an Nrf2-EMT-Notch network and experimental modulation of Nrf2 by pharmacological treatment or CRISPR/Cas9 gene editing reveal that Nrf2 stabilizes a hybrid E/M phenotype which is maximally observed in the interior region immediately behind the leading edge. We further demonstrate that the Nrf2-EMT-Notch network enhances Dll4 and Jagged1 expression at the leading edge, which correlates with the formation of leader cells and protruding tips. Altogether, our results provide direct evidence that Nrf2 acts as a phenotypic stability factor in restricting complete EMT and plays an important role in coordinating collective cancer migration.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9037689 | PMC |
| http://dx.doi.org/10.3389/fmolb.2022.807324 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Testing Ecology: Breast and Gynecological Cancer Predisposition Tests and the National Healthcare System in Spain.
Med Anthropol
December 2024
Department of Social Anthropology, University of Barcelona, Barcelona, Spain.
This research asks what is being put to the test by breast and gynecological cancer predisposition testing in Spain beyond genes or cancer. By combining document analysis and fieldwork with national healthcare professionals and drawing on the anthropology and sociology of testing, I examine how the molecular relations of these tests extend to the political economy of the national healthcare system. I show how the capacity of these tests to produce a low-risk collective has paradoxical consequences for the political economy of the national healthcare system, unsettling professionals' concerns and spotlighting what is prioritized in personalized medicine strategies.
View Article and Find Full Text PDFA Protocol for a Mixed Methods, Single-Arm, Hybrid Effectiveness-Implementation Trial Evaluating a 12-week Yoga Intervention Delivered by Videoconference for Young Adults Diagnosed With Cancer.
Glob Adv Integr Med Health
December 2024
Patient Advisory Board.
Background: Cancer among young adults (18-39 years) is relatively rare, but remains a leading cause of disability, morbidity, and mortality. Identifying strategies to support young adults' health following a diagnosis of cancer is important. Yoga may enhance health and could be delivered by videoconference.
View Article and Find Full Text PDFIncreased Early-Mortality in Children With Solid Tumors During the COVID-19 Pandemic in a Middle-Income Country.
Cancer Med
December 2024
Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of California San Diego/Rady Children's Hospital San Diego, San Diego, California, USA.
Background: Measures to control COVID-19 transmission disrupted childhood cancer care. Data on the effects of the COVID-19 pandemic on childhood cancer mortality are lacking. This study describes the impact of the pandemic on childhood cancer early-mortality (≤ 24 months).
View Article and Find Full Text PDFAn innovative Community Mobilisation and Community Incentivisation for child health in rural Pakistan (CoMIC): a cluster-randomised, controlled trial.
Lancet Glob Health
January 2025
Institute for Global Health and Development, Aga Khan University, Karachi, Pakistan; Centre for Global Child Health, The Hospital for Sick Children, Toronto, ON, Canada.
Background: Infectious diseases remain the leading cause of death among children younger than 5 years due to disparities in access and acceptance of essential interventions. The Community Mobilisation and Community Incentivisation (CoMIC) trial was designed to evaluate a customised community mobilisation and incentivisation strategy for improving coverage of evidence-based interventions for child health in Pakistan.
Methods: CoMIC was a three-arm cluster-randomised, controlled trial in rural areas of Pakistan.
Global versus local matrix remodeling drives rotational versus invasive collective migration of epithelial cells.
Dev Cell
December 2024
Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA. Electronic address:
The coordinated movement of cell collectives is essential for normal epithelial tissue development, maintenance, and cancer progression. Here, we report on a minimal 3D extracellular matrix (ECM) system wherein both invasive collective migration (ICM) and rotational collective migration (RCM) arise spontaneously from individually seeded epithelial cells of mammary and hepatic origin, regardless of whether they express adherens junctions, and lead to ductal-like and acinar-like structures, respectively. Quantitative microscopy and cellular Potts modeling reveal that initial differences in cell protrusion dynamics and matrix-remodeling localization generate RCM and ICM behavior in confining 3D ECM.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!