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Using a nationally representative survey fielded in 2009, we analyze the relationships between personality traits and various modes of political participation in South Korea. We find statistically significant relationships between personality (measured by the Five‐Factor Model) and several nonelectoral modes of participation. Openness correlates positively with protest participation, rally attendance, financial contributions to political causes, news media contacts, and political activities via the Internet. Agreeableness correlates negatively with these five participation modes as well as petition signing. Conscientiousness is positively associated with individual political acts (e.g., contacting news media and elected officials and donation), while it is negatively associated with collective actions such as participation in rally. However, we do not find any significant relationship between personality and voter turnout. Reflecting an unusually conflictual political climate of South Korea in 2008, we discuss these findings' implications focusing on the personality‐situation interactions.

MicroRNAs (miRNAs) are increasingly implicated in regulating cancer initiation and progression. In this study, two miRNAs, miR-25 and -32, are identified as p53-repressed miRNAs by p53-dependent negative regulation of their transcriptional regulators, E2F1 and MYC. However, miR-25 and -32 result in p53 accumulation by directly targeting Mdm2 and TSC1, which are negative regulators of p53 and the mTOR (mammalian target of rapamycin) pathway, respectively, leading to inhibition of cellular proliferation through cell cycle arrest. Thus, there is a recurrent autoregulatory circuit involving expression of p53, E2F1, and MYC to regulate the expression of miR-25 and -32, which are miRNAs that, in turn, control p53 accumulation. Significantly, overexpression of transfected miR-25 and -32 in glioblastoma multiforme cells inhibited growth of the glioblastoma multiforme cells in mouse brain in vivo. The results define miR-25 and -32 as positive regulators of p53, underscoring their role in tumorigenesis in glioblastoma. G lioblastoma multiforme (GBM) is by far the most common and aggressive tumor of the CNS. Despite recent improvements in surgery, radiation therapy, and cytotoxic chemotherapy, the prognosis for GBM remains grim, with median survival time <1 y after diagnosis. Of all glial tumors, GBM seems to exhibit the greatest number of genetic changes (1). The TP53 tumor suppressor gene, a transcription factor for numerous genes involved in cell cycle control, DNA repair, apoptosis, and angiogenesis (2, 3), is one of the most frequently mutated genes in human cancer. Given its profound effects in either inhibiting cell proliferation or inducing apoptosis, the expression levels of the TP53 gene product, p53, are tightly controlled through a feedback loop involving the p53 downstream target gene, Mdm2, which negatively regulates p53 through Mdm2-mediated ubiquitination of p53 (4). As such, even modest changes in the Mdm2 level can perturb the p53 protein level and affect the tumorigenesis process.MicroRNAs (miRNAs), small noncoding RNAs of ∼22 nt that mediate posttranscriptional silencing of specific target mRNAs, are being increasingly recognized as an important determinant of tumor development and progression (5). Deregulated miRNAs were suggested to exert their function in cancer through silencing of key cell fate regulators by directly binding their 3′ UTR (6, 7). Furthermore, miRNAs cooperatively function with certain transcription factors (TFs) in the regulation of mutual sets of target genes, allowing the coordinated modulation of gene expression both transcriptionally and posttranscriptionally. Specifically, it has been revealed that there is a recurring network motif in which a TF regulates the miRNA with which it cooperates in regulating a common set of targets (8).Several studies have implicated p53 in the regulation of miRNAs expression (9-11). However, most miRNAs studied so far are positively correlated with p53 expression, whereas miRNAs repressed by this tumor suppressor have rarely been studied. Here, we...

Blockade of osteoclast (OC) activity efficiently decreases tumor burden and associated bone erosion in immune-compromised animals bearing human osteolytic cancers. Here we show that modulation of anti-tumor T cell responses alters tumor growth in bone regardless of OC status, using genetic and pharmacologic models. PLCγ2−/− mice, with dysfunctional OCs and impaired dendritic cell (DC)-mediated T cell activation, had increased bone tumor burden despite protection from bone loss. In contrast, Lyn−/− mice, with more numerous OCs and a hyperactive myeloid population leading to increased T cell responses, had reduced tumor growth in bone despite enhanced osteolysis. The unexpected tumor/bone phenotype observed in PLCγ2−/− and Lyn−/− mice was transplantable, suggesting the involvement of an immune component. Consistent with this hypothesis, T cell activation diminished skeletal metastasis while T cell depletion enhanced it, even in the presence of Zoledronic acid, a potent anti-resorptive agent. Importantly, injection of antigen-specific wild-type cytotoxic CD8+ T cells in PLCγ2−/− mice or CD8+ T cell depletion in Lyn−/− mice normalized tumor growth in bone. Our findings demonstrate the important contribution of CD8+ T cells in the regulation of bone metastases regardless of OC status, thus including T cells as critical regulators of tumor growth in bone.

Primary cilia start forming within the G1 phase of the cell cycle and continue to grow as cells exit the cell cycle (G0). They start resorbing when cells re-enter the cell cycle (S phase) and are practically invisible in mitosis. The mechanisms by which cilium biogenesis and disassembly are coupled to the cell cycle are complex and not well understood. We previously identified the centrosomal phosphoprotein NDE1 as a negative regulator of ciliary length and showed that its levels inversely correlate with ciliogenesis. Here, we identify the tumor suppressor FBW7 (also known as FBXW7, CDC4, AGO, or SEL-10) as the E3 ligase that mediates the destruction of NDE1 upon entry into G1. CDK5, a kinase active in G1/G0, primes NDE1 for FBW7-mediated recognition. Cells depleted of FBW7 or CDK5 show enhanced levels of NDE1 and a reduction in ciliary length, which is corrected in cells depleted of both FBW7 or CDK5 and NDE1. These data show that cell cycle-dependent mechanisms can control ciliary length through a CDK5-FBW7-NDE1 pathway.

Down-regulation of PLCγ2 and β-catenin signaling in tumor associated myeloid cells allows for their expansion and tumor growth in mice and humans.

Collagen triple helix repeat containing-1 (CTHRC1) is a secreted protein involved in vascular remodeling, bone formation and developmental morphogenesis. CTHRC1 has recently been shown to be expressed in human cancers such as breast cancer and melanoma. In this study, we show that CTHRC1 is highly expressed in human pancreatic cancer tissues and plays a role in the progression and metastasis of the disease. CTHRC1 promoted primary tumor growth and metastatic spread of cancer cells to distant organs in orthotopic xenograft tumor mouse models. Overexpression of CTHRC1 in cancer cells resulted in increased motility and adhesiveness, whereas these cellular activities were diminished by down-regulation of the protein. CTHRC1 activated several key signaling molecules, including Src, focal adhesion kinase, paxillin, mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase and Rac1. Treatment with chemical inhibitors of Src, MEK or Rac1 and expression of dominant-negative Rac1 attenuated CTHRC1-induced cell migration and adhesion. Collectively, our results suggest that CTHRC1 has a role in pancreatic cancer progression and metastasis by regulating migration and adhesion activities of cancer cells.

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