Focal Adhesion Kinase-Dependent Role of the Soluble Form of Neurotensin Receptor-3/Sortilin in Colorectal Cancer Cell Dissociation.
The aim of the present review is to unravel the mechanisms of action of the soluble form of the neurotensin (NT) receptor-3 (NTSR3), also called Sortilin, in numerous physiopathological processes including cancer development, cardiovascular diseases and depression. Sortilin/NTSR3 is a transmembrane protein thought to exert multiple functions both intracellularly and at the level of the plasma membrane. The Sortilin/NTSR3 extracellular domain is released by shedding from all the cells expressing the protein. Although the existence of the soluble form of Sortilin/NTSR3 (sSortilin/NTSR3) has been evidenced for more than 10 years, the studies focusing on the role of this soluble protein at the mechanistic level remain rare. Numerous cancer cells, including colonic cancer cells, express the receptor family of neurotensin (NT), and particularly Sortilin/NTSR3. This review aims to summarize the functional role of sSortilin/NTSR3 characterized in the colonic cancer cell line HT29. This includes mechanisms involving signaling cascades through focal adhesion kinase (FAK), a key pathway leading to the weakening of cell-cell and cell-extracellular matrix adhesions, a series of events which could be responsible for cancer metastasis. Finally, some future approaches targeting the release of sNTSR3 through the inhibition of matrix metalloproteases (MMPs) are suggested.
Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université Côte d'Azur, 660 route des Lucioles, 06560 Valbonne, France. beraud@ipmc.cnrs.fr.
Sophie
S
Béraud-Dufour
Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université Côte d'Azur, 660 route des Lucioles, 06560 Valbonne, France. devader@ipmc.cnrs.fr.
Chistelle
C
Devader
Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université Côte d'Azur, 660 route des Lucioles, 06560 Valbonne, France. fabiennemassa@gmail.com.
Fabienne
F
Massa
Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université Côte d'Azur, 660 route des Lucioles, 06560 Valbonne, France. roulot@ipmc.cnrs.fr.
Morgane
M
Roulot
Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université Côte d'Azur, 660 route des Lucioles, 06560 Valbonne, France. coppola@ipmc.cnrs.fr.
Thierry
T
Coppola
Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Université Côte d'Azur, 660 route des Lucioles, 06560 Valbonne, France. mazella@ipmc.cnrs.fr.
Jean
J
Mazella
D033942:Adaptor Proteins, Vesicular Transport / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics* / Q000473:pathology; D002448:Cell Adhesion; D002450:Cell Communication; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D003863:Depression / Q000097:blood / Q000235:genetics* / Q000473:pathology; D051417:Focal Adhesion Kinase 1 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D019073:HT29 Cells; D006801:Humans; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D015398:Signal Transduction; D000099183:Sortilin
D033942:Adaptor Proteins, Vesicular Transport; D051417:Focal Adhesion Kinase 1; D020782:Matrix Metalloproteinases; D000099183:Sortilin; C496050:PTK2 protein, human
cancer; cell morphology; cell signaling; neurotensin; soluble neurotensin receptor-3; sortilin