P-0021 - Characterization of Niemann-Pick Type C2 protein in hepatocellular carcinoma
|Date||28 June 2014|
|Event||World GI 2014|
|Topics|| Hepatobiliary Cancers
|Citation||Annals of Oncology (2014) 25 (suppl_2): ii14-ii104. 10.1093/annonc/mdu165|
Y. Liao1, S. Hsu2, Y. Chen3
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.
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.
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.
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.