Research Papers:

RB/PLK1-dependent induced pathway by SLAMF3 expression inhibits mitosis and control hepatocarcinoma cell proliferation

Hicham Bouhlal _, Hakim Ouled-Haddou, Véronique Debuysscher, Amrathlal Rabbind Singh, Christèle Ossart, Aline Reignier, Hakim Hocini, Gregory Fouquet, Mohammed Al Baghami, Mélanie Simoes Eugenio, Eric Nguyen-Khac, Jean-Marc Regimbeau and Ingrid Marcq

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Oncotarget. 2016; 7:9832-9843. https://doi.org/10.18632/oncotarget.6954

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Hicham Bouhlal1,2, Hakim Ouled-Haddou1,*, Véronique Debuysscher1,*, Amrathlal Rabbind Singh1, Christèle Ossart1,2, Aline Reignier1,2, Hakim Hocini3, Gregory Fouquet1, Mohammed Al Baghami1,2, Mélanie Simoes Eugenio1, Eric Nguyen-Khac4, Jean-Marc Regimbeau5, Ingrid Marcq1

1Centre Universitaire de Recherche en Santé CURS, CAP-Santé (FED 4231), Université de Picardie Jules Verne, CHU Sud, Amiens, France

2Service d’Hématologie Clinique et de Thérapie Cellulaire Centre Hospitalier Universitaire Sud, Amiens, France

3IMRB, Equipe 16, Génomique Médicale, UFR de Médecine, Créteil, France

4Service Hepato-Gastroenterologie, Centre Hospitalier Universitaire Sud, Amiens, France

5Service de Chirurgie Digestive Centre Hospitalier Universitaire Sud, Amiens, France

*These authors contributed equally to this work

Correspondence to:

Hicham Bouhlal, e-mail: [email protected]

Amrathlal Rabbind Singh, e-mail: [email protected]

Ingrid Marcq, e-mail: [email protected]

Keywords: SLAMF3, HCC, retinoblastoma factor RB, polo-like kinase 1 (PLK1), mitosis

Received: June 18, 2015     Accepted: December 09, 2015     Published: January 20, 2016


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.

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