Metastasis is the chief cause of mortality from cancer, but the mechanisms leading to metastasis are poorly understood. We used a proteomics approach to screen for metastasis-associated proteins and found that collapsin response mediator protein-4 (CRMP4) expression was inversely associated with the lymph node metastasis of prostate cancer (PCa). Subsequent in vitro and in vivo studies revealed that overexpression of CRMP4 not only suppressed the invasion ability of PCa cells, but also strongly inhibited tumor metastasis in an animal model. Furthermore, methylation of a CpG island within the promoter region of the CRMP4 gene is responsible for downregulation of CRMP4 expression. Thus, in this study, we show new function of CRMP4 as a metastasissuppressor in PCa. The findings provide new mechanistic insights into metastasis and therapeutic potential for this most common male cancer.

Integration of the sphenoid and ethmoid bones during early postnatal development is poorly described in the literature. A uniquely prolonged patency of sphenoethmoidal synchondrosis or prespheno-septal synchondrosis (PSept) has been attributed to humans. However, the sphenoethmoidal junction has not been studied using a comparative primate sample. Here, we examined development of the sphenoethmoidal interface using ontogenetic samples of Old and New World monkeys, strepsirrhine primates (lemurs and lorises), and a comparative sample of other mammals. Specimens ranging from late fetal to 1 month postnatal age were studied using histology, immunohistochemistry, and micro-computed tomography methods. Our results demonstrate that humans are not unique in anterior cranial base growth at PSept, as it is patent in all newborn primates. We found two distinctions within our sample. First, nearly all primates exhibit an earlier breakdown of the nasal capsule cartilage that abuts the orbitosphenoid when compared to nonprimates. This may facilitate earlier postnatal integration of the basicranium and midface and may enhance morphological plasticity in the region. Second, the PSept exhibits a basic dichotomy between strepsirrhines and monkeys. In strepsirrhines, the PSept has proliferating chondrocytes that are primarily oriented in a longitudinal plane, as in other mammals. In contrast, monkeys have a convex anterior end of the presphenoid with a radial boundary of cartilaginous growth at PSept. Our findings suggest that the PSept acts as a "pacemaker" of longitudinal facial growth in mammals with relatively long snouts, but may also contribute to facial height and produce a relatively taller midface in anthropoid primates. Anat Rec, 300:2115-2137, 2017. © 2017 Wiley Periodicals, Inc.

Angiopoietin-1 is a promoter of physiological vasculogenesis and angiogenesis because it induces vascular branching and smooth muscle recruitment to newly formed blood vessels. However, angiopoietin-1 expression in tumours appears to be uncommon, and angiopoietin-1 overexpression in cancer cells has been reported to lead to inhibition of xenograft tumour growth. We report here that angiopoietin-1 overexpression resulted in stabilization of tumour edge-associated blood vessels, as it prevented vessel dilation and dissociation of smooth muscle cells from existing vessels. In addition, angiopoietin-1 stimulated an infiltration of mesenchymal cells into the tumours, such that the coverage of microvessels by pericytes increased markedly, and the cancer cells were separated into small masses by the host stroma. The rates of both cancer cell proliferation and apoptosis decreased significantly in the presence of angiopoietin-1. Tie2, the receptor for angiopoietin-1, was found to be present in vascular smooth muscle cells in culture in addition to endothelial cells. These findings suggest that a vascular stabilization effect of angiopoietin-1 accounts for the inhibition of tumour growth.

Increasing evidence indicates that long non-coding RNAs (lncRNAs) act as important regulatory factors in tumor progression. However, their roles in breast cancer remain largely unknown. In present studies, we identified aberrantly expressed long intergenic non-coding RNA APOC1P1-3 (lincRNA-APOC1P1-3) in breast cancer by microarray, verified it by quantitative real-time PCR, and assessed methylation status in the promoter region by pyrosequencing. We also investigated the biological functions with plasmid transfection and siRNA silencing experiments, and further explored their mechanisms by RNA pull-down and RNA immunoprecipitation to identify binding proteins. We found that 224 lncRNAs were upregulated in breast cancer, whereas 324 were downregulated. The lincRNA-APOC1P1-3 was overexpressed in breast cancer, which was related to tumor size and hypomethylation in its promoter region. We also found that APOC1P1-3 could directly bind to tubulin to decrease α-tubulin acetylation, to inactivate caspase-3, and to inhibit apoptosis. This study demonstrates that overexpression of APOC1P1-3 can inhibit breast cancer apoptosis.

Background: Mammaglobin (MAM) has been used as a specific molecular marker for breast cancer diagnosis. Recently, several groups of researchers proposed a number of therapeutic strategies targeting this molecule. Some of the strategies are based upon an essential but not demonstrated hypothesis -mammaglobin is associated with the surface of breast cancer cells, which strongly disputes the therapeutic strategies.