American Association for Cancer Research
Browse
- No file added yet -

Supplemental Figures and Table from Spatiotemporal Loss of NF1 in Schwann Cell Lineage Leads to Different Types of Cutaneous Neurofibroma Susceptible to Modification by the Hippo Pathway

Download (13.56 MB)
journal contribution
posted on 2023-04-03, 21:43 authored by Zhiguo Chen, Juan Mo, Jean-Philippe Brosseau, Tracey Shipman, Yong Wang, Chung-Ping Liao, Jonathan M. Cooper, Robert J. Allaway, Sara J.C. Gosline, Justin Guinney, Thomas J. Carroll, Lu Q. Le

Supplemental Figure 1 shows the immunohistochemistry for nerve fibers in cNF. Supplemental Figure 2 shows the role of NF1 heterozygosity in neurofibroma development. Supplemental Figure 3 shows the effect of male Vs female on plexiform neurofibroma development. Supplemental Table 1 lists the genotype and phenotype of H7;Nf1mut and control mice.

Funding

Dermatology Research Training Program

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Find out more...

Wellcome Fund

NIH

U.S. Department of Defense

Giorgio Foundation

History

ARTICLE ABSTRACT

Neurofibromatosis type 1 (NF1) is a cancer predisposition disorder that results from inactivation of the tumor suppressor neurofibromin, a negative regulator of RAS signaling. Patients with NF1 present with a wide range of clinical manifestations, and the tumor with highest prevalence is cutaneous neurofibroma (cNF). Most patients harboring cNF suffer greatly from the burden of those tumors, which have no effective medical treatment. Ironically, none of the numerous NF1 mouse models developed so far recapitulate cNF. Here, we discovered that HOXB7 serves as a lineage marker to trace the developmental origin of cNF neoplastic cells. Ablating Nf1 in the HOXB7 lineage faithfully recapitulates both human cutaneous and plexiform neurofibroma. In addition, we discovered that modulation of the Hippo pathway acts as a “modifier” for neurofibroma tumorigenesis. This mouse model opens the doors for deciphering the evolution of cNF to identify effective therapies, where none exist today. This study provides insights into the developmental origin of cNF, the most common tumor in NF1, and generates the first mouse model that faithfully recapitulates both human cutaneous and plexiform neurofibroma. The study also demonstrates that the Hippo pathway can modify neurofibromagenesis, suggesting that dampening the Hippo pathway could be an attractive therapeutic target.This article is highlighted in the In This Issue feature, p. 1

Usage metrics

    Cancer Discovery

    Categories

    Keywords

    CarcinogenesisAnimal models of carcinogenesisOncogenes & Tumor SuppressorsTumor suppressor genes

    Licence

    CC BY

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC