P-0021 - Characterization of Niemann-Pick Type C2 protein in hepatocellular carcinoma

Date 28 June 2014
Event World GI 2014
Session Poster Session
Topics Hepatobiliary Cancers
Translational Research
Presenter Yi-Jen Liao
Citation Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165
Authors Y. Liao1, S. Hsu2, Y. Chen3
  • 1School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei/TW
  • 2Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei/TW
  • 3Department of Microbiology, College of Medicine, Kaohsiung Medical University, Kaohsiung/TW

Abstract

Introduction

Niemann-Pick Type C2 (NPC2) plays an important role in the regulation of intracellular cholesterol homeostasis via direct binding with free cholesterol. However, little is known about the significance of NPC2 in liver cancer.

Methods

The expression of NPC2 in liver cancer patients (n = 50) were detected using IHC staining and Q-PCR. The associations between NPC2 expression and clinicopathological characteristics were compared using Student's t-test for continuous variables and Fisher's exact test for categorical variables. NPC2 knockdown in sk-hep1 cells were subjected to cell proliferation, migration and in-vivo tumorigenesis. Cell lysates were collected to detect proteins involving in MAPK signaling pathway.

Results

NPC2 is abundantly expressed in normal liver, but is down-regulated in human HCC tissues. The patients with NPC2 down-regulation expressed much higher α-fetoprotein (p = 0.03), multiple tumor type (p = 0.02), vascular invasion (p = 0.01), later pathological stage (p = 0.03) and shorter survival rate (p = 0.011). In addition, knockdown NPC2 in liver cancer cell lines promote cell proliferation, migration and in-vivo tumorigenesis. To identify the NPC2-dependent mechanism, we emphasized on the status of MAPK signaling. Sustained phosphorylation of ERK1/2 has been observed in NPC2 knockdown cells. However, p38 and JNK did not activate in NPC2 knockdown cells.

Conclusion

Our study suggests that NPC2 may play an important role in negatively regulate ERK1/2 activation in liver cancer. NPC2 may thus represent a new strategy for the treatment of liver cancer.