@article{4ad34f6b3ddf48ada9db36b11f2ff6d5,
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.",
keywords = "MPNST, NF1, cancer stem cells, neural crest, neurofibromatosis, neurofibrosarcoma",
author = "Daochun Sun and Xie, {Xuanhua P.} and Xiyuan Zhang and Zilai Wang and Sait, {Sameer Farouk} and Iyer, {Swathi V.} and Chen, {Yu Jung} and Rebecca Brown and Laks, {Dan R.} and Chipman, {Mollie E.} and Shern, {Jack F.} and Parada, {Luis F.}",
note = "Funding Information: We would like to thank all members of the Parada laboratory for helpful suggestions and discussion. We thank the Memorial Sloan Kettering Cancer Center (MSKCC) Molecular Cytology and Weill Cornell Genomics cores for their assistance. We thank Markku Miettinen, MD, of the Laboratory of Pathology, National Cancer Institute (NCI)/NIH, for the diagnosis of ANNUBP analyzed in this study. We would like to acknowledge Alicia Maria Pedraza, Samhita Bapat, and Yanjiao Li for their contributions to this project. D.S. is a recipient of the NF Research Initiative Early Career Award ( GENFD 0001371278 ), and L.F.P. is a recipient of the Investigator-Initiated Research Award, Congressionally Directed Medical Research Programs from the U.S. Department of Defense ( W81XWH-16-1-0186 ); NCI Specialized Programs of Research Excellence (SPORE) U54 CA196519-01 ; R01: CA131313 ; and NIH /NCI Cancer Center Support Grant P30 CA008748 and holds the Albert C. Foster Chair in Cancer Research. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = aug,
day = "5",
doi = "10.1016/j.stem.2021.04.029",
language = "English",
volume = "28",
pages = "1397--1410.e4",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "8",
}