Posters
Presenting Author Academic/Professional Position
Medical Student
Academic Level (Author 1)
Faculty
Discipline/Specialty (Author 1)
Pediatrics
Academic Level (Author 2)
Graduate Student
Discipline/Specialty (Author 2)
Neurology
Academic Level (Author 3)
Graduate Student
Discipline/Specialty (Author 3)
Pediatrics
Academic Level (Author 4)
Medical Student
Academic Level (Author 5)
Staff
Presentation Type
Poster
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background: Neuroblastoma (NB) is the most common extracranial solid tumor in children. Two of the earliest known genetic drivers of NB are the oncogene MYCN and receptor tyrosine kinase ALK. While animal models show MYCN and mutationally active ALK F1174L can accelerate NB tumorigenesis, the mechanism of this cooperation is unknown. This study applied a human stem cell-based model to elucidate how ALK cooperates with MYCN to accelerate tumorigenesis of NB.
Methods: Induced pluripotent stem cells (iPSCs) were engineered with doxycycline-inducible MYCN and constitutively active ALKF1174L. These iPSCs were differentiated into trunk neural crest cells (tNCCs) and orthotopically transplanted into immunocompromised mice. Transcriptomic analysis and functional assays, including RNA seq and CRISPR interference were conducted to assess the molecular drivers of tumorigenesis. Western blot was performed to interrogate proteins in pathways of interest.
Results: Tumors derived from MYCN/ALK F1174L iPSCs exhibited mesenchymal characteristics, with upregulation of periostin (POSTN) and activation of WNT signaling. POSTN knockdown impaired adhesion, migration, and consequently proliferation of tumor cells, while WNT inhibition reduced POSTN expression. Conversely, activation of WNT restored growth in POSTN-deficient cells. A feedforward loop between POSTN and WNT signaling was identified as critical for ALK-driven neuroblastoma progression.
Conclusions: This study demonstrates that ALK and MYCN cooperate through a POSTN-WNT signaling axis to promote neuroblastoma growth. Targeting this pathway may provide new therapeutic strategies for high-risk neuroblastoma by discovering that POSTN and WNT signal through a feedforward loop.
Recommended Citation
Huang, Miller; Fang, Wanqi; Farrel, Alvin; Li, Linwei; Corredor, Tania Porras; Asgharzadeh, Shahab; Maris, John; and Weiss, William A., "ALK drives neuroblastoma tumorigenesis via upregulation of POSTN and activation of WNT and STAT3 signaling" (2025). Research Symposium. 92.
https://scholarworks.utrgv.edu/somrs/2025/posters/92
Included in
ALK drives neuroblastoma tumorigenesis via upregulation of POSTN and activation of WNT and STAT3 signaling
Background: Neuroblastoma (NB) is the most common extracranial solid tumor in children. Two of the earliest known genetic drivers of NB are the oncogene MYCN and receptor tyrosine kinase ALK. While animal models show MYCN and mutationally active ALK F1174L can accelerate NB tumorigenesis, the mechanism of this cooperation is unknown. This study applied a human stem cell-based model to elucidate how ALK cooperates with MYCN to accelerate tumorigenesis of NB.
Methods: Induced pluripotent stem cells (iPSCs) were engineered with doxycycline-inducible MYCN and constitutively active ALKF1174L. These iPSCs were differentiated into trunk neural crest cells (tNCCs) and orthotopically transplanted into immunocompromised mice. Transcriptomic analysis and functional assays, including RNA seq and CRISPR interference were conducted to assess the molecular drivers of tumorigenesis. Western blot was performed to interrogate proteins in pathways of interest.
Results: Tumors derived from MYCN/ALK F1174L iPSCs exhibited mesenchymal characteristics, with upregulation of periostin (POSTN) and activation of WNT signaling. POSTN knockdown impaired adhesion, migration, and consequently proliferation of tumor cells, while WNT inhibition reduced POSTN expression. Conversely, activation of WNT restored growth in POSTN-deficient cells. A feedforward loop between POSTN and WNT signaling was identified as critical for ALK-driven neuroblastoma progression.
Conclusions: This study demonstrates that ALK and MYCN cooperate through a POSTN-WNT signaling axis to promote neuroblastoma growth. Targeting this pathway may provide new therapeutic strategies for high-risk neuroblastoma by discovering that POSTN and WNT signal through a feedforward loop.
