Hyaluronic acid fuels pancreatic cancer cell growth Journal Article
| Authors: | Kim, P. K.; Halbrook, C. J.; Kerk, S. A.; Radyk, M.; Wisner, S.; Kremer, D. M.; Sajjakulnukit, P.; Andren, A.; Hou, S. W.; Trivedi, A.; Thurston, G.; Anand, A.; Yan, L.; Salamanca-Cardona, L.; Welling, S. D.; Zhang, L.; Pratt, M. R.; Keshari, K. R.; Ying, H.; Lyssiotis, C. A. |
| Article Title: | Hyaluronic acid fuels pancreatic cancer cell growth |
| Abstract: | 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. © 2021, eLife Sciences Publications Ltd. All rights reserved. |
| Keywords: | immunohistochemistry; signal transduction; controlled study; microscopy; nonhuman; pancreas cancer; cell proliferation; mouse; animal tissue; cell death; cell viability; cell growth; fluorescence; animal experiment; animal model; in vitro study; tumor xenograft; enzyme linked immunosorbent assay; histology; xenograft; western blotting; glycosylation; bovine serum albumin; real time polymerase chain reaction; hyaluronic acid; cytokeratin; nutrient; oligonucleotide; acetic acid; metabolite; glutamine; methanol; tumor microenvironment; colony formation; pancreatic ductal adenocarcinoma; liquid chromatography-mass spectrometry; tumor metabolism; mycoplasma; crystal violet; phosphate buffered saline; cancer metabolism; article; glcnac; mercaptoethanol; cell proliferation assay; fetal bovine serum; gfat1; hexosamine biosynthetic pathway; nagk |
| Journal Title: | eLife |
| Volume: | 10 |
| ISSN: | 2050-084X |
| Publisher: | eLife Sciences Publications Ltd. |
| Date Published: | 2021-12-24 |
| Start Page: | e62645 |
| Language: | English |
| DOI: | 10.7554/eLife.62645 |
| PUBMED: | 34951587 |
| PROVIDER: | scopus |
| PMCID: | PMC8730721 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2022 -- Source: Scopus |
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