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

Oncotarget
Hicham BouhlalIngrid Marcq

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 ...Continue Reading

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Citations

Jan 5, 2017·BMC Genomics·Constantinos G BroustasSally A Amundson
May 31, 2018·Cancer Biomarkers : Section a of Disease Markers·Liang ZhangYi Zhu
Apr 18, 2018·Oncotarget·Gregory FouquetHicham Bouhlal

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Methods Mentioned

BETA
xenografts
transfection
surgical resection
flow cytometry
PCR
electrophoresis
flow

Software Mentioned

Prism
FACSDiva
GraphPad

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