2. Academic Validation
  3. Neuropeptide Y/Y5 Receptor Pathway Stimulates Neuroblastoma Cell Motility Through RhoA Activation

Neuropeptide Y/Y5 Receptor Pathway Stimulates Neuroblastoma Cell Motility Through RhoA Activation

  • Front Cell Dev Biol. 2021 Feb 17:8:627090. doi: 10.3389/fcell.2020.627090.
Nouran Abualsaud 1 2 3,  Lindsay Caprio 4,  Susana Galli 1,  Ewa Krawczyk 5,  Lamia Alamri 6,  Shiya Zhu 1,  G Ian Gallicano 1,  Joanna Kitlinska 1
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, DC, United States.
  • 2 Cell Therapy and Cancer Research Department, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.
  • 3 King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
  • 4 Department of Human Science, School of Nursing and Health Studies, Georgetown University, Washington, DC, United States.
  • 5 Center for Cell Reprogramming, Georgetown University Medical Center, Washington, DC, United States.
  • 6 Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, United States.
PMID: 33681186 DOI: 10.3389/fcell.2020.627090
Abstract

Neuropeptide Y (NPY) has been implicated in the regulation of cellular motility under various physiological and pathological conditions, including Cancer dissemination. Yet, the exact signaling pathways leading to these effects remain unknown. In a pediatric malignancy, neuroblastoma (NB), high NPY release from tumor tissue associates with metastatic disease. Here, we have shown that NPY stimulates NB cell motility and invasiveness and acts as a chemotactic factor for NB cells. We have also identified the Y5 receptor (Y5R) as the main NPY receptor mediating these actions. In NB tissues and cell cultures, Y5R is highly expressed in migratory cells and accumulates in regions of high RhoA activity and dynamic Cytoskeleton remodeling. Y5R stimulation activates RhoA and results in Y5R/RhoA-GTP interactions, as shown by pull-down and proximity ligation assays, respectively. This is the first demonstration of the role for the NPY/Y5R axis in RhoA activation and the subsequent Cytoskeleton remodeling facilitating cell movement. These findings implicate Y5R as a target in anti-metastatic therapies for NB and Other cancers expressing this receptor.

Keywords

RhoA; cell migration; neuroblastoma; neuropeptide Y; neuropeptide Y receptor Y5.

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