Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By implantation of BSp73 ascites cells in a subcutaneous site and subsequent subcutaneous passage of either the local tumor node or metastatic lung tissue, variants were obtained which differed with respect to morphology and to metastatic capacity. The highly metastasizing variant ASML showed spherical morphology in culture, while the nonmetastatic variant AS showed adhesion and spreading. Upon cloning it was observed that colonies with fully expressed morphotypes were readily obtained from solid tissue of both variants. Parental ascites as well as the tumor line derived from the primary solid tumor gave rise to stable expression of either morphotype only after prolonged culturing. Mixing of established clones did not result in an interclonal adaptation of growth rates in vivo. Further characterization of variants AS and ASML revealed marked differences in the outer cell surface. Adhesion of AS cells onto plastic was found to be mediated by fibronectin, laminin and 4 out of 5 collagen types. ASML cells showed adhesion only with collagen type III at higher concentrations. Cytogenetic analysis revealed that the adaptation of BSp73 cells to ascitic growth ultimately led to an increase in chromosome numbers, and this was conserved in ASML cells (modal number 63, range 49-74). AS cells on the other hand showed a modal number of 47 (range 45-49). The chromosome count distribution was rather narrow in ascites cells in vivo, but it was very broad in clones derived thereof, indicating that diversity was obtained in culture rather than in vivo. The data are compatible with the assumption that the nonmetastatic variant was not preexisting in BSp73 ascites but represents a stable phenotype which infrequently arises in a particular microenvironment by chromosome loss from a hyperdiploid parental population.
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PMID:Clonal analysis of diversity in the BSp73 rat tumor. 406 7

During the past decade, the molecular mechanisms in the process of tumor progression, including metastasis and angiogenesis, have become better understood. Cancer metastasis consists of multiple, complex interacting steps. Each of these steps is crucial and limiting, since a failure to complete any one prevents the tumor cell from producing a metastasis. Detachment from the solid tumor by loosening the intercellular junctions and proteolysis of the extracellular matrix enables tumor cells to enter blood- and lymph vessels. The intravasation into the circulation is supported by the secretion of angiogenic factors, which induce degradation of the basal membrane in blood vessels. Adhesion to endothelial cells, extravasation from the circulation, and induction of angiogenesis are further essential steps for completing the metastatic process. Furthermore, it is well known that once a tumor cell has entered circulation, it will survive only by evasion of the immune system. The systematic identification of tumor antigens opens up new possibilities for immunotherapeutic approaches.
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PMID:[Molecular genetic principles of progression of malignant diseases]. 1087 46

Previous studies proposed that myosin-Va regulates apoptosis by sequestering pro-apoptotic Bmf to the actin cytoskeleton through dynein light chain-2 (DLC2). Adhesion loss or other cytoskeletal perturbations would unleash Bmf, allowing it to bind and inhibit pro-survival Bcl2 proteins. Here, we demonstrated that overexpression of a myosin-Va medial tail fragment (MVaf) harboring the binding site for DLC2 dramatically decreased melanoma cell viability. Morphological and molecular changes, including surface blebbing, mitochondrial outer membrane permeabilization, cytochrome-c and Smac release, as well as caspase-9/-3 activation and DNA fragmentation indicated that melanoma cells died of apoptosis. Immobilized MVaf interacted directly with DLCs, but complexed MVaf/DLCs did not interact with Bmf. Overexpression of DLC2 attenuated MVaf-induced apoptosis. Thus, we suggest that, MVaf induces apoptosis by sequestering DLC2 and DLC1, thereby unleashing the pair of sensitizer and activator BH3-only proteins Bmf and Bim. Murine embryonic fibroblasts (MEFs) lacking Bim and Bmf or Bax and Bak were less sensitive to apoptosis caused by MVaf expression than wild-type MEFs, strengthening the putative role of the intrinsic apoptotic pathway in this response. Finally, MVaf expression attenuated B16-F10 solid tumor growth in mice, suggesting that this peptide may be useful as an apoptosis-inducing tool for basic and translational studies.
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PMID:A myosin-Va tail fragment sequesters dynein light chains leading to apoptosis in melanoma cells. 2351 16

Hepatocellular carcinoma (HCC) is the fifth most common solid tumor in the world and the third leading cause of cancer-associated deaths. A Sleeping Beauty-mediated transposon mutagenesis screen previously identified mutations that cooperate with MYC to accelerate liver tumorigenesis. This revealed a tumor suppressor role for Steroid Receptor Coactivator 2/Nuclear Receptor Coactivator 2 (Src-2/Ncoa2) in liver cancer. In contrast, SRC-2 promotes survival and metastasis in prostate cancer cells, suggesting a tissue-specific and context-dependent role for SRC-2 in tumorigenesis. To determine if genetic loss of SRC-2 is sufficient to accelerate MYC-mediated liver tumorigenesis, we bred Src-2-/- mice with a MYC-induced liver tumor model and observed a significant increase in liver tumor burden. RNA sequencing of liver tumors and in vivo chromatin immunoprecipitation assays revealed a set of direct target genes that are bound by SRC-2 and exhibit downregulated expression in Src-2-/- liver tumors. We demonstrate that activation of SHP (Small Heterodimer Partner), DKK4 (Dickkopf-4), and CADM4 (Cell Adhesion Molecule 4) by SRC-2 suppresses tumorigenesis in vitro and in vivo. These studies suggest that SRC-2 may exhibit oncogenic or tumor suppressor activity depending on the target genes and nuclear receptors that are expressed in distinct tissues and illuminate the mechanisms of tumor suppression by SRC-2 in liver.
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PMID:SRC-2-mediated coactivation of anti-tumorigenic target genes suppresses MYC-induced liver cancer. 2964 18