TY - JOUR TI - Hyaluronic acid fuels pancreatic cancer cell growth AU - Kim, Peter K AU - Halbrook, Christopher J AU - Kerk, Samuel A AU - Radyk, Megan AU - Wisner, Stephanie AU - Kremer, Daniel M AU - Sajjakulnukit, Peter AU - Andren, Anthony AU - Hou, Sean W AU - Trivedi, Ayush AU - Thurston, Galloway AU - Anand, Abhinav AU - Yan, Liang AU - Salamanca-Cardona, Lucia AU - Welling, Samuel D AU - Zhang, Li AU - Pratt, Matthew R AU - Keshari, Kayvan R AU - Ying, Haoqiang AU - Lyssiotis, Costas A A2 - Finley, Lydia WS A2 - White, Richard M VL - 10 PY - 2021 DA - 2021/12/24 SP - e62645 C1 - eLife 2021;10:e62645 DO - 10.7554/eLife.62645 UR - https://doi.org/10.7554/eLife.62645 AB - Rewired metabolism is a hallmark of pancreatic ductal adenocarcinomas (PDA). Previously, we demonstrated that PDA cells enhance glycosylation precursor biogenesis through the hexosamine biosynthetic pathway (HBP) via activation of the rate limiting enzyme, glutamine-fructose 6-phosphate amidotransferase 1 (GFAT1). Here, we genetically ablated GFAT1 in human PDA cell lines, which completely blocked proliferation in vitro and led to cell death. In contrast, GFAT1 knockout did not preclude the growth of human tumor xenografts in mice, suggesting that cancer cells can maintain fidelity of glycosylation precursor pools by scavenging nutrients from the tumor microenvironment. We found that hyaluronic acid (HA), an abundant carbohydrate polymer in pancreatic tumors composed of repeating N-acetyl-glucosamine (GlcNAc) and glucuronic acid sugars, can bypass GFAT1 to refuel the HBP via the GlcNAc salvage pathway. Together, these data show HA can serve as a nutrient fueling PDA metabolism beyond its previously appreciated structural and signaling roles. KW - pancreatic cancer KW - tumor metabolism KW - tumor microenvironment KW - extracellular matrix KW - hyaluronic acid KW - hexosamine biosynthetic pathway JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -