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Review
. 2021 Aug 11;26(16):4849.
doi: 10.3390/molecules26164849.

Orexins/Hypocretins and Cancer: A Neuropeptide as Emerging Target

Couvineau Alain  1 , Nicole Pascal  1 , Gratio Valérie  1 , Voisin Thierry  1
Affiliations
Review

Orexins/Hypocretins and Cancer: A Neuropeptide as Emerging Target

Couvineau Alain et al. Molecules. .

Abstract

Over 20 years ago, orexin neuropeptides (Orexin-A/hypocretin-1 and Orexin-B/hypocretins-2) produced from the same precursor in hypothalamus were identified. These two neurotransmitters and their receptors (OX1R and OX1R), present in the central and peripheral nervous system, play a major role in wakefulness but also in drug addiction, food consumption, homeostasis, hormone secretion, reproductive function, lipolysis and blood pressure regulation. With respect to these biological functions, orexins were involved in various pathologies encompassing narcolepsy, neurodegenerative diseases, chronic inflammations, metabolic syndrome and cancers. The expression of OX1R in various cancers including colon, pancreas and prostate cancers associated with its ability to induce a proapoptotic activity in tumor cells, suggested that the orexins/OX1R system could have a promising therapeutic role. The present review summarizes the relationship between cancers and orexins/OX1R system as an emerging target.

Keywords: GPCR; apoptosis; cancer; gastroenterology; neuropeptide; orexins.

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Conflict of interest statement

Authors don’t have any conflict of interest.

Figures

Figure 1
Figure 1
Structure of orexins and their receptors and main signaling pathways activated by orexins in cancer cells. DsB, disulfide bridge; IP3, inositol tri-phosphate; PLC, phospholipase; SHP2, Src homology 2 (SH2) domains of SH2-containing phosphatase 2; cAMP, cyclic adenosine monophosphate; Akt, protein kinase B; JNKs, c-jun N-terminal kinases; ERK1/2, extracellular signal-regulated kinase 1 and 2; ITIM, immunoreceptor tyrosine-based motifs; Src, Src kinases.
Figure 2
Figure 2
Impact of orexins/OXR system on cancers. SHP2, Src homology 2 (SH2) domains of SH2-containing phosphatase 2; Akt, protein kinase B; ITIM, immunoreceptor tyrosine-based motifs.
See this image and copyright information in PMC

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