Stem-like cells drive NF1-associated MPNST functional heterogeneity and tumor progression Journal Article


Authors: Sun, D.; Xie, X. P.; Zhang, X.; Wang, Z.; Sait, S. F.; Iyer, S. V.; Chen, Y. J.; Brown, R.; Laks, D. R.; Chipman, M. E.; Shern, J. F.; Parada, L. F.
Article Title: Stem-like cells drive NF1-associated MPNST functional heterogeneity and tumor progression
Abstract: NF1-associated malignant peripheral nerve sheath tumors (MPNSTs) are the major cause of mortality in neurofibromatosis. MPNSTs arise from benign peripheral nerve plexiform neurofibromas that originate in the embryonic neural crest cell lineage. Using reporter transgenes that label early neural crest lineage cells in multiple NF1 MPNST mouse models, we discover and characterize a rare MPNST cell population with stem-cell-like properties, including quiescence, that is essential for tumor initiation and relapse. Following isolation of these cells, we derive a cancer-stem-cell-specific gene expression signature that includes consensus embryonic neural crest genes and identify Nestin as a marker for the MPNST cell of origin. Combined targeting of cancer stem cells along with antimitotic chemotherapy yields effective tumor inhibition and prolongs survival. Enrichment of the cancer stem cell signature in cognate human tumors supports the generality and relevance of cancer stem cells to MPNST therapy development. © 2021 Elsevier Inc.
Keywords: neurofibromatosis; neural crest; mpnst; nf1; cancer stem cells; neurofibrosarcoma
Journal Title: Cell Stem Cell
Volume: 28
Issue: 8
ISSN: 1934-5909
Publisher: Cell Press  
Date Published: 2021-08-05
Start Page: 1397
End Page: 1410.e4
Language: English
DOI: 10.1016/j.stem.2021.04.029
PUBMED: 34010628
PROVIDER: scopus
PMCID: PMC8349880
DOI/URL:
Notes: Article -- Export Date: 1 September 2021 -- Source: Scopus
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MSK Authors
  1. Luis F Parada
    21 Parada
  2. Zilai Wang
    7 Wang
  3. Daochun Sun
    12 Sun
  4. Xuanhua Xie
    9 Xie
  5. Dan R Laks
    6 Laks
  6. Swathi Venkartraman Iyer
    2 Iyer
  7. Yu-Jung Chen
    3 Chen
  8. Rebecca Meg Brown
    2 Brown