title: Tumour co-expression of apelin and its receptor is the basis of an autocrine loop involved in the growth of colon adenocarcinomas.
abstract: Using a cancer profiling array, our laboratory has shown that apelin gene is up-regulated in half of colon adenocarcinomas. We have therefore postulated that apelin signalling might play a prominent role in the growth of colon tumours. We first confirmed by immunohistochemistry that apelin peptide is overexpressed in human colon adenomas and adenocarcinomas. We also observed a significant overexpression of apelin receptor (APJ) in adjacent sections. We then demonstrated that several colorectal cancer cell lines also expressed apelin and its receptor, the highest gene and peptide expression being detected in LoVo cells. In this cell line, the expression and functionality of apelin receptor were revealed by apelin-induced adenylyl cyclase inhibition and Akt phosphorylation. In addition, apelin clearly protected LoVo cells from apoptosis by inactivating a caspase-dependent pathway and decreasing the degradation of poly ADP ribose polymerase protein (PARP). Finally, treatment of these tumour cells by the (F13A)apelin13 receptor antagonist significantly reduced their proliferation rate. Altogether, these data suggest the existence of an autocrine loop by which constitutive activation of apelin signalling should participate in the growth of colon adenocarcinomas. Accordingly, apelin signalling is a promising pharmacological target for the treatment of human colon adenomas and adenocarcinomas.
authors: Cancer Research Center of Toulouse, UMR 1037 INSERM - Université Toulouse III, CHU Rangueil, Bât L3, 1, Avenue Jean Poulhès, BP 84225, 31432 Toulouse, France.
authors: François-Xavier
authors: FX
authors: Picault
authors: Cancer Research Center of Toulouse, UMR 1037 INSERM - Université Toulouse III, CHU Rangueil, Bât L3, 1, Avenue Jean Poulhès, BP 84225, 31432 Toulouse, France.
authors: Carline
authors: C
authors: Chaves-Almagro
authors: Center of Biological Resources, CHU Rangueil, Bât L2, 1, Avenue Jean Poulhès, BP 84225, 31432 Toulouse, France.
authors: Fabrice
authors: F
authors: Projetti
authors: Cancer Research Center of Toulouse, UMR 1037 INSERM - Université Toulouse III, CHU Rangueil, Bât L3, 1, Avenue Jean Poulhès, BP 84225, 31432 Toulouse, France.
authors: Hervé
authors: H
authors: Prats
authors: Cancer Research Center of Toulouse, UMR 1037 INSERM - Université Toulouse III, CHU Rangueil, Bât L3, 1, Avenue Jean Poulhès, BP 84225, 31432 Toulouse, France.
authors: Bernard
authors: B
authors: Masri
authors: Cancer Research Center of Toulouse, UMR 1037 INSERM - Université Toulouse III, CHU Rangueil, Bât L3, 1, Avenue Jean Poulhès, BP 84225, 31432 Toulouse, France. Electronic address: yves.audigier@inserm.fr.
authors: Yves
authors: Y
authors: Audigier
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000073861:Apelin; D000075244:Apelin Receptors; D017209:Apoptosis / Q000502:physiology; D019898:Autocrine Communication; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C115436:APLN protein, human; C104575:APLNR protein, human; D000073861:Apelin; D000075244:Apelin Receptors; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled
keywords: Apoptosis; Colon cancer; G protein-coupled receptors; Signalisation; Tumour growth