Integrin signaling in cancer: bidirectional mechanisms and therapeutic opportunities.
Bidirectional signaling mechanisms
Integrin
Integrin-targeting drugs
Tumorigenesis
Journal
Cell communication and signaling : CCS
ISSN: 1478-811X
Titre abrégé: Cell Commun Signal
Pays: England
ID NLM: 101170464
Informations de publication
Date de publication:
28 09 2023
28 09 2023
Historique:
received:
07
07
2023
accepted:
09
08
2023
medline:
4
10
2023
pubmed:
29
9
2023
entrez:
28
9
2023
Statut:
epublish
Résumé
Integrins are transmembrane receptors that possess distinct ligand-binding specificities in the extracellular domain and signaling properties in the cytoplasmic domain. While most integrins have a short cytoplasmic tail, integrin β4 has a long cytoplasmic tail that can indirectly interact with the actin cytoskeleton. Additionally, 'inside-out' signals can induce integrins to adopt a high-affinity extended conformation for their appropriate ligands. These properties enable integrins to transmit bidirectional cellular signals, making it a critical regulator of various biological processes.Integrin expression and function are tightly linked to various aspects of tumor progression, including initiation, angiogenesis, cell motility, invasion, and metastasis. Certain integrins have been shown to drive tumorigenesis or amplify oncogenic signals by interacting with corresponding receptors, while others have marginal or even suppressive effects. Additionally, different α/β subtypes of integrins can exhibit opposite effects. Integrin-mediated signaling pathways including Ras- and Rho-GTPase, TGFβ, Hippo, Wnt, Notch, and sonic hedgehog (Shh) are involved in various stages of tumorigenesis. Therefore, understanding the complex regulatory mechanisms and molecular specificities of integrins are crucial to delaying cancer progression and suppressing tumorigenesis. Furthermore, the development of integrin-based therapeutics for cancer are of great importance.This review provides an overview of integrin-dependent bidirectional signaling mechanisms in cancer that can either support or oppose tumorigenesis by interacting with various signaling pathways. Finally, we focus on the future opportunities for emergent therapeutics based on integrin agonists. Video Abstract.
Identifiants
pubmed: 37770930
doi: 10.1186/s12964-023-01264-4
pii: 10.1186/s12964-023-01264-4
pmc: PMC10537162
doi:
Substances chimiques
Hedgehog Proteins
0
Integrins
0
Types de publication
Video-Audio Media
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
266Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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