title: RB/PLK1-dependent induced pathway by SLAMF3 expression inhibits mitosis and control hepatocarcinoma cell proliferation.
abstract: Polo-like kinase PLK1 is a cell cycle protein that plays multiple roles in promoting cell cycle progression. Among the many roles, the most prominent role of PLK1 is to regulate the mitotic spindle formation checkpoint at the M-phase. Recently we reported the expression of SLAMF3 in Hepatocytes and show that it is down regulated in tumor cells of hepatocellular carcinoma (HCC). We also show that the forced high expression level of SLAMF3 in HCC cells controls proliferation by inhibiting the MAPK ERK/JNK and the mTOR pathways. In the present study, we provide evidence that the inhibitory effect of SLAMF3 on HCC proliferation occurs through Retinoblastoma (RB) factor and PLK1-dependent pathway. In addition to the inhibition of MAPK ERK/JNK and the mTOR pathways, expression of SLAMF3 in HCC retains RB factor in its hypophosphorylated active form, which in turn inactivates E2F transcription factor, thereby repressing the expression and activation of PLK1. A clear inverse correlation was also observed between SLAMF3 and PLK expression in patients with HCC. In conclusion, the results presented here suggest that the tumor suppressor potential of SLAMF3 occurs through activation of RB that represses PLK1. We propose that the induction of a high expression level of SLAMF3 in cancerous cells could control cellular mitosis and block tumor progression.
authors.affiliation: Centre Universitaire de Recherche en Santé CURS, CAP-Santé (FED 4231), Université de Picardie Jules Verne, CHU Sud, Amiens, France.|Service d'Hématologie Clinique et de Thérapie Cellulaire Centre Hospitalier Universitaire Sud, Amiens, France.
authors.forename: Hicham
authors.initials: H
authors.lastname: Bouhlal
authors.affiliation: Centre Universitaire de Recherche en Santé CURS, CAP-Santé (FED 4231), Université de Picardie Jules Verne, CHU Sud, Amiens, France.
authors.forename: Hakim
authors.initials: H
authors.lastname: Ouled-Haddou
authors.affiliation: Centre Universitaire de Recherche en Santé CURS, CAP-Santé (FED 4231), Université de Picardie Jules Verne, CHU Sud, Amiens, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Debuysscher
authors.affiliation: Centre Universitaire de Recherche en Santé CURS, CAP-Santé (FED 4231), Université de Picardie Jules Verne, CHU Sud, Amiens, France.
authors.forename: Amrathlal Rabbind
authors.initials: AR
authors.lastname: Singh
authors.affiliation: Centre Universitaire de Recherche en Santé CURS, CAP-Santé (FED 4231), Université de Picardie Jules Verne, CHU Sud, Amiens, France.|Service d'Hématologie Clinique et de Thérapie Cellulaire Centre Hospitalier Universitaire Sud, Amiens, France.
authors.forename: Christèle
authors.initials: C
authors.lastname: Ossart
authors.affiliation: Centre Universitaire de Recherche en Santé CURS, CAP-Santé (FED 4231), Université de Picardie Jules Verne, CHU Sud, Amiens, France.|Service d'Hématologie Clinique et de Thérapie Cellulaire Centre Hospitalier Universitaire Sud, Amiens, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Reignier
authors.affiliation: IMRB, Equipe 16, Génomique Médicale, UFR de Médecine, Créteil, France.
authors.forename: Hakim
authors.initials: H
authors.lastname: Hocini
authors.affiliation: Centre Universitaire de Recherche en Santé CURS, CAP-Santé (FED 4231), Université de Picardie Jules Verne, CHU Sud, Amiens, France.
authors.forename: Gregory
authors.initials: G
authors.lastname: Fouquet
authors.affiliation: Centre Universitaire de Recherche en Santé CURS, CAP-Santé (FED 4231), Université de Picardie Jules Verne, CHU Sud, Amiens, France.|Service d'Hématologie Clinique et de Thérapie Cellulaire Centre Hospitalier Universitaire Sud, Amiens, France.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al Baghami
authors.affiliation: Centre Universitaire de Recherche en Santé CURS, CAP-Santé (FED 4231), Université de Picardie Jules Verne, CHU Sud, Amiens, France.
authors.forename: Mélanie Simoes
authors.initials: MS
authors.lastname: Eugenio
authors.affiliation: Service Hepato-Gastroenterologie, Centre Hospitalier Universitaire Sud, Amiens, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Nguyen-Khac
authors.affiliation: Service de Chirurgie Digestive Centre Hospitalier Universitaire Sud, Amiens, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Regimbeau
authors.affiliation: Centre Universitaire de Recherche en Santé CURS, CAP-Santé (FED 4231), Université de Picardie Jules Verne, CHU Sud, Amiens, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Marcq
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism*; D000071176:Signaling Lymphocytic Activation Molecule Family / Q000378:metabolism*; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D016160:Retinoblastoma Protein; D000071176:Signaling Lymphocytic Activation Molecule Family; D000097869:Polo-Like Kinase 1; C430423:LY9 protein, human
keywords: HCC; SLAMF3; mitosis; polo-like kinase 1 (PLK1); retinoblastoma factor RB