Effects of STC1 overexpression on tumorigenicity and metabolism of hepatocellular carcinoma
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Cherry CT Leung1 and Chris KC Wong1
1Department of Biology, Hong Kong Baptist University, Hong Kong SAR, China
Chris KC Wong, email: email@example.com
Keywords: xenograft; tumor mass; boyden chamber; rpS6; AMPK
Received: August 30, 2017 Accepted: October 28, 2017 Published: December 21, 2017
Stanniocalcin-1 (STC1) is a paracrine factor associated with inflammation and carcinogenesis. Using clinicopathological data, we previously reported that a greater expression of STC1 in hepatocellular carcinoma (HCC) was significantly correlated with smaller tumor size. The underlying mechanism on the correlation is not known. In this study, using a metastatic HCC cell-line (MHCC-97L, P) and lentiviral vector mediated-STC1 overexpression, the inoculation of STC1-overexpressing MHCC-97L (S1) cells in a nude mice xenograft model demonstrated reductions in tumor mass and volume. As compared with P cells, S1 cells exhibited epithelial phenotype with significantly lower plating efficiency and reduced migratory and proliferative potential. Using coulter counter for cell-sizing, S1 cells (17.6 μm) were significantly smaller than P cells (19.6 μm). Western blot analysis revealed that S1 cells exhibited reduced expression level of phosphorylated ribosomal protein S6 (p-rpS6). Moreover, an inhibition of the upstream kinase p70S6K was evident with the dephosphorylation of Thr389 in the linker domain of the kinase. The inhibition of p70S6K/p-rpS6 pathway was accompanied with reduced cellular ATP level and increase of p-AMPK in S1 cells. Significantly lower rates of glycolysis and extracellular O2 consumption in S1 cells exhibited a lower cellular energy status. Since a faster rate of ATP production is essential to support cancer growth and metastasis, the present study identified the effect of STC1-overexpression on reducing energy metabolism, leading to an activation of AMPK pathway but an inhibition of p70S6K/p-rpS6 signaling to reduce tumor growth.
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