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Related Concept Videos

Ligand Binding Sites02:40

Ligand Binding Sites

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Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
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Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
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Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
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G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
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Proteomics to Identify Proteins Interacting with P2X2 Ligand-Gated Cation Channels
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Transcriptome-Derived Ligand-Receptor Interactome of Major PitNET Subgroups.

Sai Batchu1, Michael Joseph Diaz2, Aashay Patel2

  • 1Cooper Medical School, Rowan University, Camden, New Jersey, United States.

Journal of Neurological Surgery. Part B, Skull Base
|July 5, 2024
PubMed
Summary

Pituitary neuroendocrine tumors (PitNETs) exhibit diverse ligand-receptor interactions. Understanding these signaling pathways, like cortisol and CCL25, is crucial for developing targeted therapies for PitNET subtypes.

Keywords:
Cushing's diseasePitNETacromegalyclinical subtypeligand-receptor interactionsrelative crosstalk score

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Area of Science:

  • Endocrinology
  • Oncology
  • Bioinformatics

Background:

  • Pituitary neuroendocrine tumors (PitNETs) are rare skull base tumors with significant invasive potential.
  • The ligand-receptor (LR) interactome of PitNET subtypes is poorly understood, limiting therapeutic strategies.
  • This study investigates LR interactions across different PitNET clinical presentations.

Purpose of the Study:

  • To analyze the LR interactome of PitNETs using in silico methods.
  • To identify distinct signaling pathways in PitNET subtypes associated with acromegaly, Cushing's disease, prolactinoma, and non-functioning tumors.
  • To explore tumor-to-tumor, tumor-to-stroma, and stroma-to-tumor signaling axes.

Main Methods:

  • Acquisition of previously published PitNET gene expression data from ArrayExpress.
  • Analysis of LR interactions using a crosstalk score approach.
  • In silico modeling of ligand-receptor complexes.

Main Results:

  • Cortisol (CORT) ligand was involved in tumor-to-tumor signaling across most PitNET subtypes, except prolactinomas which showed CORT depletion.
  • CCL25 ligand was implicated in tumor-to-stroma signaling, with silent PitNETs showing CCL25 depletion.
  • All PitNET subtypes showed stromal vasoactive intestinal polypeptide and DEFB103B ligand interactions.
  • Cushing's disease PitNETs had high stromal CD274 expression, while prolactinomas had low expression and high IL10RA expression.

Conclusions:

  • Ligand-receptor crosstalk analysis reveals significant diversity in PitNET subtypes and tumor compartments.
  • Specific signaling pathways and ligand-receptor interactions differ across clinical presentations.
  • Further research is needed to validate these findings and determine their clinical significance for PitNET treatment.