2. Academic Validation
  3. Inflammatory monocytes constrain YAP-induced cell proliferation

Inflammatory monocytes constrain YAP-induced cell proliferation

  • Sci Adv. 2026 Jun 26;12(26):eaee8580. doi: 10.1126/sciadv.aee8580.
Serrena Singh 1 2,  Nareh Tahmasian 3,  Jia-Jun Liu 4,  Wenjia Wang 4,  Lucas Haas 1 2,  Yingdong Zhu 1 2,  Magdalena M Griswold 5,  Nina N Brodsky 5,  Silvia Liu 4,  Brian T Kalish 3 6 7 8,  Dean Yimlamai 1 2
Affiliations

Affiliations

  • 1 Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Yale School of Medicine, New Haven, CT 06520, USA.
  • 2 Yale Liver Center, Department of Medicine, Yale School of Medicine, New Haven, CT 06520, USA.
  • 3 Program in Neuroscience and Mental Health, SickKids Research Institute, Toronto, ON M5G 1L7, Canada.
  • 4 Organ Pathobiology and Therapeutics Institute, Department of Pharmacology and Chemical Biology, Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • 5 Section of Critical Care Medicine, Department of Pediatrics, Yale School of Medicine; New Haven, CT 06520, USA.
  • 6 Department of Molecular Genetics, University of Toronto, Toronto, ON M5G 1A8, Canada.
  • 7 Division of Neonatology, Department of Paediatrics, Hospital for Sick Children, Toronto, ON, Canada.
  • 8 Division of Neonatology, Department of Pediatrics, Boston Children's Hospital, Boston 02115, MA, USA.
PMID: 42341114 DOI: 10.1126/sciadv.aee8580
Abstract

YAP and its paralog, TAZ, are transcriptional coactivators of the Hippo pathway that regulate cell growth. Their structural distinctiveness suggests important independent functional differences. To investigate this further, we generated YAP- and TAZ-predominant clones in the liver and followed their long-term behavior. YAP clones rapidly dedifferentiate cells into a stem cell-like state with inflammatory immune cell recruitment followed by their clearance. In contrast, TAZ clones promote an anti-inflammatory immune environment, resulting in their long-term maintenance, massive organ growth, and increased mortality. YAP clones recruit inflammatory blood-derived monocytes, which, if inhibited, permits YAP clonal growth. Consistent with these results, patients with YAPHigh colorectal Cancer (CRC) had a 67% 5-year survival rate, whereas patients with TAZHigh CRC did not survive to 5 years. Similar trends were seen in patients with hepatocellular carcinoma. These findings underscore the importance of understanding the intrinsic differences in YAP and TAZ biology as independent drivers of disease.

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