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ALK upregulates POSTN and WNT signaling to drive neuroblastoma.
Huang, Miller; Fang, Wanqi; Farrel, Alvin; Li, Linwei; Chronopoulos, Antonios; Nasholm, Nicole; Cheng, Bo; Zheng, Tina; Yoda, Hiroyuki; Barata, Megumi J; Porras, Tania; Miller, Matthew L; Zhen, Qiqi; Ghiglieri, Lisa; McHenry, Lauren; Wang, Linyu; Asgharzadeh, Shahab; Park, JinSeok; Gustafson, W Clay; Matthay, Katherine K; Maris, John M; Weiss, William A.
Afiliação
  • Huang M; Children's Hospital Los Angeles, Cancer and Blood Disease Institutes, and The Saban Research Institute, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. Electronic address: mhuang@chla.usc.edu.
  • Fang W; Children's Hospital Los Angeles, Cancer and Blood Disease Institutes, and The Saban Research Institute, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Farrel A; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Li L; Children's Hospital Los Angeles, Cancer and Blood Disease Institutes, and The Saban Research Institute, Los Angeles, CA, USA.
  • Chronopoulos A; Children's Hospital Los Angeles, Cancer and Blood Disease Institutes, and The Saban Research Institute, Los Angeles, CA, USA.
  • Nasholm N; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Cheng B; Children's Hospital Los Angeles, Cancer and Blood Disease Institutes, and The Saban Research Institute, Los Angeles, CA, USA.
  • Zheng T; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Yoda H; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Barata MJ; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Porras T; Children's Hospital Los Angeles, Cancer and Blood Disease Institutes, and The Saban Research Institute, Los Angeles, CA, USA.
  • Miller ML; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Zhen Q; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Ghiglieri L; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • McHenry L; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Wang L; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
  • Asgharzadeh S; Children's Hospital Los Angeles, Cancer and Blood Disease Institutes, and The Saban Research Institute, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Park J; Children's Hospital Los Angeles, Cancer and Blood Disease Institutes, and The Saban Research Institute, Los Angeles, CA, USA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Gustafson WC; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Departments of Pediatrics and Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Matthay KK; Departments of Pediatrics and Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • Maris JM; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
  • Weiss WA; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA; Departments of Pediatrics and Neurological Surgery, University of California, San Francisco, San
Cell Rep ; 43(3): 113927, 2024 Mar 26.
Article em En | MEDLINE | ID: mdl-38451815
ABSTRACT
Neuroblastoma is the most common extracranial solid tumor of childhood. While MYCN and mutant anaplastic lymphoma kinase (ALKF1174L) cooperate in tumorigenesis, how ALK contributes to tumor formation remains unclear. Here, we used a human stem cell-based model of neuroblastoma. Mis-expression of ALKF1174L and MYCN resulted in shorter latency compared to MYCN alone. MYCN tumors resembled adrenergic, while ALK/MYCN tumors resembled mesenchymal, neuroblastoma. Transcriptomic analysis revealed enrichment in focal adhesion signaling, particularly the extracellular matrix genes POSTN and FN1 in ALK/MYCN tumors. Patients with ALK-mutant tumors similarly demonstrated elevated levels of POSTN and FN1. Knockdown of POSTN, but not FN1, delayed adhesion and suppressed proliferation of ALK/MYCN tumors. Furthermore, loss of POSTN reduced ALK-dependent activation of WNT signaling. Reciprocally, inhibition of the WNT pathway reduced expression of POSTN and growth of ALK/MYCN tumor cells. Thus, ALK drives neuroblastoma in part through a feedforward loop between POSTN and WNT signaling.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Proteína Tirosina Quinases / Neuroblastoma Limite: Humans Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores Proteína Tirosina Quinases / Neuroblastoma Limite: Humans Idioma: En Revista: Cell Rep Ano de publicação: 2024 Tipo de documento: Article