TGFβ-dependent signaling drives tumor growth and aberrant extracellular matrix dynamics in NF1-associated plexiform neurofibroma
dc.contributor.author | Abu-Sultanah, Mohannad | |
dc.contributor.author | Zhou, Zhuan | |
dc.contributor.author | Jiang, Chunhui | |
dc.contributor.author | Mitchell, Dana K. | |
dc.contributor.author | Bessler, Waylan K. | |
dc.contributor.author | Jiang, Li | |
dc.contributor.author | Li, Xiaohong | |
dc.contributor.author | Qian, Shaomin | |
dc.contributor.author | Smith, Abbi E. | |
dc.contributor.author | Mang, Henry E. | |
dc.contributor.author | White, Emily E. | |
dc.contributor.author | Ciesielski, Marisa D. | |
dc.contributor.author | Hickey, Brooke E. | |
dc.contributor.author | Brewster, Kylee M. | |
dc.contributor.author | Sandusky, George E. | |
dc.contributor.author | Masters, Andi | |
dc.contributor.author | Angus, Steven P. | |
dc.contributor.author | Clapp, D. Wade | |
dc.contributor.author | Le, Lu Q. | |
dc.contributor.author | Rhodes, Steven D. | |
dc.contributor.department | Pediatrics, School of Medicine | |
dc.date.accessioned | 2025-07-17T11:35:08Z | |
dc.date.available | 2025-07-17T11:35:08Z | |
dc.date.issued | 2025 | |
dc.description.abstract | Plexiform neurofibromas (PNFs) are benign tumors of the peripheral nervous system that represent a major source of morbidity in neurofibromatosis type 1 (NF1). A substantial proportion of patients do not respond to current therapies or experience intolerable side effects. Transcriptomic characterization of murine and human PNF at bulk and single-cell resolution identified transforming growth factor-β (TGFβ) signaling as a key upstream regulator, driving aberrant basement membrane (BM) protein production by neoplastic Schwann cells and Fbs. Conditional TGFβ1 overexpression in Nf1-deficient Schwann cells driven by Hoxb7-Cre promoted PNF growth and malignant transformation in vivo. Conversely, pharmacologic inhibition of the type I TGFβ receptor (TGFβRI) reduced PNF tumor burden in Nf1 mutant mice. Proteomic characterization of the extracellular matrix (ECM) showed reduced BM proteins upon TGFβRI inhibition. These findings implicate TGFβ as a potential therapeutic target in PNF and provide insights into the role of TGFβ signaling in orchestrating ECM dynamics in the PNF microenvironment. | |
dc.eprint.version | Final published version | |
dc.identifier.citation | Abu-Sultanah M, Zhou Z, Jiang C, et al. TGFβ-dependent signaling drives tumor growth and aberrant extracellular matrix dynamics in NF1-associated plexiform neurofibroma. Sci Adv. 2025;11(25):eadu0772. doi:10.1126/sciadv.adu0772 | |
dc.identifier.uri | https://hdl.handle.net/1805/49548 | |
dc.language.iso | en_US | |
dc.publisher | American Association for the Advancement of Science | |
dc.relation.isversionof | 10.1126/sciadv.adu0772 | |
dc.relation.journal | Science Advances | |
dc.rights | Attribution-NonCommercial 4.0 International | en |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | |
dc.source | PMC | |
dc.subject | Neurofibromatosis 1 | |
dc.subject | Plexiform neurofibroma | |
dc.subject | Schwann cells | |
dc.subject | Cell proliferation | |
dc.title | TGFβ-dependent signaling drives tumor growth and aberrant extracellular matrix dynamics in NF1-associated plexiform neurofibroma | |
dc.type | Article |