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The GRPR signaling axis in cancer: Molecular mechanisms and oncogenic outcomes
Júlia Caroline Marcolin1, Martina Lichtenfels2, Rafael Roesler3
1Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Porto Alegre, RS, Brazil; Graduate Program in Biological Sciences: Pharmacology and Therapeutics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Abstract:
The gastrin-releasing peptide (GRP) and its receptor (GRPR) constitute a biologically versatile signaling axis with essential physiological roles and growing relevance in cancer biology. GRPR is frequently expressed across multiple tumor types, where its activation modulates key cellular processes associated with malignant progression. Through engagement of diverse intracellular effectors and extensive crosstalk with receptor tyrosine kinases and other signaling systems, GRPR regulates pathways controlling tumor cell proliferation, survival, migration, invasion, angiogenesis, and transcriptional reprogramming. This review provides a comprehensive overview of the molecular mechanisms underlying GRPR-mediated signaling in cancer, integrating evidence from different tumor models. Importantly, the antitumor effects observed following pharmacological inhibition or genetic silencing of GRPR further underscore its therapeutic relevance. Collectively, these findings position GRPR as a central signaling integrator in tumor progression and a promising target for diagnostic, prognostic, and therapeutic strategies in oncology.
Insights
Gastrin-releasing peptide receptor (GRPR) signaling is crucial in cancer, regulating tumor progression. Inhibiting GRPR shows therapeutic potential for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- The gastrin-releasing peptide (GRP) and its receptor (GRPR) signaling axis plays vital roles in physiology.
- GRPR is increasingly recognized for its significance in cancer biology, being expressed in various tumor types.
Purpose of the Study:
- To provide a comprehensive review of GRPR-mediated signaling mechanisms in cancer.
- To integrate evidence from diverse tumor models regarding GRPR's role.
- To highlight the therapeutic potential of targeting GRPR.
Main Methods:
- Literature review integrating evidence from multiple tumor models.
- Analysis of molecular mechanisms of GRPR signaling.
- Examination of studies on GRPR inhibition and silencing.
Main Results:
- GRPR activation influences key cancer processes like proliferation, survival, migration, invasion, and angiogenesis.
- GRPR signaling involves complex intracellular pathways and crosstalk with other signaling systems, including receptor tyrosine kinases.
- Pharmacological or genetic inhibition of GRPR demonstrates significant antitumor effects.
Conclusions:
- GRPR acts as a central signaling integrator in tumor progression.
- GRPR represents a promising therapeutic target for cancer diagnostics, prognostics, and treatments.
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