Gene expression is closely related to cell survival, cell-to-cell adhesion or cell spreading; therefore, HCCs with high 18F-FDG uptake appear to have more aggressive biological properties than those with low uptake.

Hexokinase type II (HK II) is the key enzyme for maintaining increased glycolysis in cancer cells where it is overexpressed. 3-bromopyruvate (3-BrPA), an inhibitor of HK II, induces cell death in cancer cells. To elucidate the molecular mechanism of 3-BrPA-induced cell death, we used the hepatoma cell lines SNU449 (low expression of HKII) and Hep3B (high expression of HKII). 3-BrPA induced ATP depletion-dependent necrosis and apoptosis in both cell lines. 3-BrPA increased intracellular reactive oxygen species (ROS) leading to mitochondrial dysregulation. NAC (N-acetyl-L: -cysteine), an antioxidant, blocked 3-BrPA-induced ROS production, loss of mitochondrial membrane potential and cell death. 3-BrPA-mediated oxidative stress not only activated poly-ADP-ribose (PAR) but also translocated AIF from the mitochondria to the nucleus. Taken together, 3-BrPA induced ATP depletion-dependent necrosis and apoptosis and mitochondrial dysregulation due to ROS production are involved in 3-BrPA-induced cell death in hepatoma cells.

Apoptosis is a normal process by which cells are eliminated during embryonic development and in adult life. 1 Disruption of this process results in illegitimate cell survival and causes developmental abnormalities or diseases such as cancer. It is now believed that many cancers are the consequence of failed apoptotic cell death rather than enhanced cell growth.Chemotherapeutic drugs, such as etoposide, adriamycin, mitoxanthrone, cisplatin, and 5-fluorouracil (5-FU), have been shown to induce apoptosis in several leukemias and solid tumors. 2 However, the mechanism by which apoptosis is caused by these drugs is not understood completely. Recent studies have shown that the Fas/Fas ligand (FasL) system plays a key role in the execution of apoptosis. 3 Fas belongs to the tumor necrosis factor receptor family. Binding of Fas by its agonistic antibodies or by the natural ligand of the receptor, FasL, induces trimerization of the receptors, which then causes the subsequent binding of Fas-associated protein with death domain (FADD) to Fas. The Fas-bound FADD then recruits FADD-like interleukin-1-converting enzyme, which contains the protease domain that related to caspase family proteases. The binding of FADD-like interleukin-

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Vimentin, an intermediate filament protein induced during epithelialto-mesenchymal transition, is known to regulate cell migration and invasion. However, it is still unclear how vimentin controls such behaviors. In this study, we aimed to find a new integrin regulator by investigating the H-Ras-mediated integrin suppression mechanism. Through a proteomic screen using the integrin β3 cytoplasmic tail protein, we found that vimentin might work as an effector of H-Ras signaling. H-Ras converted filamentous vimentin into aggregates near the nucleus, where no integrin binding can occur. In addition, an increase in the amount of vimentin filaments accessible to the integrin β3 tail enhanced talin-induced integrin binding to its ligands by inducing integrin clustering. In contrast, the vimentin head domain, which was found to bind directly to the integrin β3 tail and compete with endogenous vimentin filaments for integrin binding, induced nuclear accumulation of vimentin filaments and reduced the amount of integrin-ligand binding. Finally, we found that expression of the vimentin head domain can reduce cell migration and metastasis. From these data, we suggest that filamentous vimentin underneath the plasma membrane is involved in increasing integrin adhesiveness, and thus regulation of the vimentin-integrin interaction might control cell adhesion.