Objective: The Wnt/β-catenin pathway is involved in the development of hepatocellular carcinoma (HCC) and malignant events such as the epithelial-mesenchymal transition (EMT), metastasis, and invasion. Studies have illustrated that the inhibition of tankyrases (TNKS) antagonizes Wnt/β-catenin signaling in many cancer cells. Methods: The expression levels of proteins related to the Wnt/β-catenin pathway and EMT were analyzed by immunohistochemistry in HCC tissue and paired adjacent normal tissue (n = 10), and in an analysis of The Cancer Genome Atlas (TCGA) data. Additionally, after treatment of HCC cell lines with TNKS1/2 small interfering RNA (siRNA) and a novel TNKS inhibitor (NVP-TNKS656), cell viability, cell clone formation, wound-healing, and cell invasion assays were performed. Results: Higher expression of β-catenin, TNKS, vimentin, and N-cadherin was observed in HCC tissue compared to adjacent normal tissue, but lower expression of E-cadherin was found in HCC tissue. These findings were also observed in the TCGA analysis. In addition, TNKS inhibition (using TNKS1/2 siRNA and NVP-TNKS656) not only abrogated the proliferation of the HCC cell lines but also suppressed metastasis, invasion, and EMT phenotypic features. Moreover, the mechanisms related to TNKS inhibition in HCC probably involved the stabilization of AXIN levels and the downregulation of β-catenin, which mediates EMT marker expression. Conclusion: The TNKS/β-catenin signaling pathway is a potential anti-proliferation and anti-metastatic target in HCC.

Background The upregulation of ADAM17 has been reported to be associated with invasion and metastasis in various tumors, however the molecular mechanism of ADAM17 in the progression of hepatocellular carcinoma (HCC) remain to be clarified. Human matrix metalloproteinase 21 (MMP21), the newest member of the MMP gene family, has been suggested to play an important role in embryogenesis and tumor progression. So far, nothing is known about the relationship between ADAM17 and MMP21. Methods In this study, the expression level of ADAM17 and MMP21 in HCC tissues was measured by immunohistochemistry. The Scratch wounding assay and Transwell were used to identify the invasion and metastasis ability. ELISA was used to evaluate the production of MMP21. Coimmunoprecipitation experiments demonstrated a direct association between ADAM17 and MMP21. HPLC was used to confirmed that ADAM17 participated in the maturation of MMP21. Results Our present data indicated that ADAM17 and MMP21 was significantly upregulated in human HCC tissues. Knockdown of ADAM17 in HCC inhibited cell invasion and metastasis. Moreover, ADAM17 regulates the secretion and expression of MMP21. Furthermore we discovered a direct association between ADAM17 and MMP21, and we also found MMP21 prodomain could be cleaved by ADAM17. Conclusion Our data suggest that ADAM17 plays an important role in the development of HCC invasion and metastasis and this function may be implement by MMP21.

For the purpose of ameliorating the temperature resistance of nanopolymer particles, a kind of hyper-crosslinked polymer, named Zr-AM/NVP/AMPS [main monomer acrylamide (AM), functional monomers N-vinylpyrrolidone (NVP), and 2-acrylamide-2-methylpropanesulfonic acid (AMPS)] with size varying from 100 to 170 nm and special doublecross-linked architectures, were prepared through inverse emulsion copolymerization of organic cross-linking agent N, Nmethylene bis acrylamide (MBA), and metal cross-linking agent zirconium acetate (Zr) as a cross-linking system, ammonium persulfate (KPS) as the initiator for the first time. The surface morphology, pore structure, particle size distribution, crosslinking architecture and element distribution of nanoparticles were fully characterized with several means including SEM, TEM, LPSA, BET, FT-IR, 13 CNMR, elemental analysis, and long-term thermal stability. The SEM, TEM, LPSA, and BET experimental results indicate that the nanopolymer particle exhibits regular spherical shape and smooth surface, has mesopores ranging from 4.9−7.1 nm with a typical diameter centered (BJH pore size distribution) at ∼5.7 nm. FT-IR, 13 CNMR, and elemental analysis experimental results indicate that the monodisperse mesoporous networks nanopolymer particles were crosslinked by AM, AMPS, NVP, MBA, and Zr. Compared to the ordinary AM/NVP/AMPS nanoparticles, significantly enhanced high-temperature thermal stability was found under 150 °C. A core displacement experiment showed how the nanopolymer particles could effectively plug the porous media for water control and oil recovery improvement even after aging at 150 °C for three months. Oil recovery is increased by 13% on the basis of water flooding. Zr-AM/NVP/AMPS nanoparticles with doublecross-linked architectures can be a great help for petroleum engineers to better apply this deep profile control and flooding technology.

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