Unchecked Growth in 3D Culture Identified as Key Feature of Immortalized Cells

Scientists at Cedars-Sinai Medical Center have discovered that unchecked growth in three-dimensions (3D) in culture is a key feature of immortalized cells on the path to malignant transformation, potentially leading to cancer. According to the study, expression of genes driving 3D growth, but not 2D growth, is more specific to cancer development and may serve as a potential target for prevention. The research identified a set of 85 genes that were specifically lost in 3D cultures, with 11 genes prioritized for bladder cancer. Notably, the gene MAPK1 remained relevant across various cancer types and was validated as a specific target for 3D growth inhibition.

Key Takeaways:

• Unchecked growth in 3D culture is a key feature of immortalized cells on the path to malignant transformation.
• Expression of genes driving 3D growth, but not 2D growth, is more specific to cancer development and may serve as a potential target for prevention.
• CRISPR depletion screens identified 85 genes that were specifically lost in 3D cultures, with 11 genes prioritized for bladder cancer.
• The gene MAPK1 remained relevant across various cancer types and was validated as a specific target for 3D growth inhibition.
• Single gene in vitro validation confirmed that MAPK1 inhibition was specific to 3D growth.
• Inhibition of MAPK1 by Ulixertinib led to human bladder cancer growth inhibition in both 3D in vitro and in vivo models.
• Screening for genes specifically driving 3D growth in immortalized cells may provide targets for both prevention and early therapy in bladder and other cancers while potentially limiting therapeutic toxicity.

Statistics:

• 85 genes were identified as specifically lost in 3D cultures.
• 11 genes were prioritized for bladder cancer.
• 3D in vitro and in vivo models showed efficacy of MAPK1 inhibition.
• Ulixertinib, an orally active MAPK1 inhibitor, was used to inhibit MAPK1 in human bladder cancer cells.
• 10.1038/s41419-025-07719-5 is the DOI for the research article "Genes driving three-dimensional growth of immortalized cells and cancer" published in Cell Death and Disease.

Sources:

• "Genes driving three-dimensional growth of immortalized cells and cancer". Cell Death and Disease, 2025, 16(1):1-11. (Cell Death and Disease - http://www.nature.com/cddis/index.html).
• http://www.nature.com/cddis/index.html
• Cell Death and Disease is published by Nature Publishing Group.
• A free version of this journal article is available at https://doi-org.sdpl.idm.oclc.org/10.1038/s41419-025-07719-5.