ArticleCell communication and signaling : CCS2026
Activation of the pituitary adenylate cyclase-activating polypeptide type I receptor promotes neuroblastoma proliferation and migration through distinct G protein pathways.
Article in Cell communication and signaling : CCS, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
The pituitary adenylate cyclase-activating polypeptide type I receptor (PAC1R) is a class B G protein-coupled receptor implicated in a variety of physiological and pathological processes, including cancer. While PAC1R has been reported to act as either an oncogene or a tumor suppressor in a context-dependent manner, its role in neuroblastoma remains largely unexplored. In this study, we identify PAC1R as being selectively overexpressed in neuroblastoma and strongly associated with poor patient prognosis, supporting its potential as a prognostic biomarker. Functionally, PAC1R activation by PACAP38 promoted neuroblastoma cell proliferation and migration through distinct G protein signaling pathways. Pharmacological inhibition and CRISPR/Cas9-mediated gene knockout revealed that proliferation is mediated by the Gαs/EPAC/AKT-ERK axis, whereas migration requires cooperative signaling through Gα12/13- and Gαq-dependent activation of the RhoA-ROCK pathway. Comprehensive signaling analyses using TRUPATH and BRET-based biosensors demonstrated broad activation of Gαs, Gαq/11, and Gα13 by PACAP38 and PACAP27, while maxadilan and VIP displayed biased agonism toward Gαs and Gα15. β-Arrestin recruitment assays further showed that PACAP38 exhibits greater potency and efficacy than PACAP27. Among three PAC1R inhibitors tested, AMG-301, a clinical-stage monoclonal antibody, most effectively inhibited PAC1R-mediated G protein activation, calcium mobilization, RhoA signaling, proliferation, and migration. Together, these findings establish PAC1R as a functionally significant and druggable target in neuroblastoma, highlight its context-dependent signaling plasticity, and support the rationale for PAC1R-targeted therapeutic strategies in high-risk neuroblastoma.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.