Authors
Kevin M Tharp, Sangwoo Park, Greg A Timblin, Alicia L Richards, Jordan A Berg, Nicholas M Twells, Nicholas M Riley, Kyle Alvarez, Allen Lee, Egan L Peltan, D Judy Shon, Erica Stevenson, Kimberly Tsui, Francesco Palomba, Austin E Y T Lefebvre, Ross W Soens, Jaya L Thangaraj, Nadia M E Ayad, Joseph A Rhodenhiser, Johanna Ten Hoeve, Kevin Healy, Michelle Digman, Andrew Dillin, Nevan J Krogan, Carolyn R Bertozzi, Dan S Kaufman, Sanju Sinha, Danielle L Swaney, Lara K Mahal, Jason R Cantor, Matthew J Paszek, Valerie M Weaver
Published in
Science advances. Volume 12. Issue 32. Pages eaeb1136. Aug 07, 2026. Epub Aug 07, 2026.
Abstract
Altered glucose metabolism is an auspicious feature of solid tumors, but is it an intrinsic property of tumor cells or a metabolic adaptation to the tumor microenvironment? Using normal epithelial cells cultured in a physiological culture medium under conditions that mimic the physical properties of healthy or cancerous tissues, we establish multiomics relationships between the biochemical and physical properties of the microenvironment and its impact on biosynthetic outputs of altered glucose metabolism. We find that microenvironmental properties, such as hyperglycemia, can affect the composition and thickness of the epithelial glycocalyx, in part through the activity of mechanosensitive stress responses associated with Heat Shock Factor 1 (HSF1). Because glycocalyx thickness alters immune surveillance of epithelial-origin tumor cells, we examined the relationship between the HSF1-hyperglycemia axis in human breast tumors and validate it as a druggable vulnerability to license natural killer cell lethality against cancer cells.
PMID:
42566549
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.
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