Cooper CS, Park M, Blair DG, Tainsky MA, Huebner K, Croce CM et al.. Molecular cloning of a new transforming gene from a chemically transformed human cell line. Nature 311: 29-33

Nature (Impact Factor: 41.46). 09/1984; 311(5981):29-33. DOI: 10.1038/311029a0
Source: PubMed


Molecular cloning of the transforming gene from a chemically transformed human osteosarcoma-derived cell line enables the gene to be mapped to chromosome 7 (7p11.4-7qter) and by this criterion and by direct hybridization to be shown to be unrelated to known oncogenes.

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    • "c-Met, a transmembrane tyrosine kinase encoded by a c-met proto-oncogene [1], [2], has emerged as a key determinant of brain tumor growth [3]. c-Met is expressed in a wide variety of brain tumors, including glioblastoma multiforme (GBM) and medulloblastoma (MB), and its expression level frequently correlates with tumors histological grade and poor patient prognosis [4]. "
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    ABSTRACT: Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) induced apoptosis specifically in tumor cells. However, with approximately half of all known tumor lines being resistant to TRAIL, the identification of TRAIL sensitizers and their mechanism of action become critical to broadly use TRAIL as a therapeutic agent. In this study, we explored whether c-Met protein contributes to TRAIL sensitivity. We found a direct correlation between the c-Met expression level and TRAIL resistance. We show that the knock down c-Met protein, but not inhibition, sensitized brain tumor cells to TRAIL-mediated apoptosis by interrupting the interaction between c-Met and TRAIL cognate death receptor (DR) 5. This interruption greatly induces the formation of death-inducing signaling complex (DISC) and subsequent downstream apoptosis signaling. Using intracranially implanted brain tumor cells and stem cell (SC) lines engineered with different combinations of fluorescent and bioluminescent proteins, we show that SC expressing a potent and secretable TRAIL (S-TRAIL) have a significant anti-tumor effect in mice bearing c-Met knock down of TRAIL-resistant brain tumors. To our best knowledge, this is the first study that demonstrates c-Met contributes to TRAIL sensitivity of brain tumor cells and has implications for developing effective therapies for brain tumor patients.
    Full-text · Article · Apr 2014 · PLoS ONE
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    • "The Receptor Tyrosine Kinase, Met, was first discovered as the TPR-MET oncogenic fusion protein in 1984 by Cooper et al. (Cooper et al., 1984). A few years later Met was found to belong to the family of RTKs (Park et al., 1987). "
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    ABSTRACT: Deregulated signalling of the Receptor Tyrosine Kinase (RTK), Met, and/or its ligand HGF have been associated with cancer formation and progression to metastasis, with Met/HGF often overexpressed or mutated. Thus, Met has become a major target for cancer therapy and its inhibition is currently being tested in the clinic. It has recently become evident that, instead of signalling at the plasma membrane only, Met signals post-internalisation from endosomal compartments. Thus, Met endocytic trafficking is required for the full activation of signals such as Gab1, ERK 1/2, STAT3 and Rac1, all implicated in cell survival, invasion and metastasis. Modifications in the balance between degradation and recycling of Met may also impinge on Met signalling. Moreover, oncogenic Met mutations in the kinase domain trigger constitutive Met internalisation/recycling, leading to "endosomal signalling" and consequent cell transformation. Using Met as an example, this review outlines the evidence that the molecular mechanisms regulating trafficking and endosomal signalling may be exploited to design future cancer therapies.
    Full-text · Article · Jan 2014 · The international journal of biochemistry & cell biology
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    • "Nup98 is also a well indentifed proto-oncogene in leukemia [10] and is also part of a recurrent chromosomal translocation event observed in acute myeloid leukemia patients [11]. TPR (translocated promoter region and part of the NPC), was named after its initial isolation from a carcinogen treated asteogenic sarcoma cell line as part of a chromosomal translocation event that fused the N-terminal sequence of TPR to the kinase domain of the proto-oncogene Met [12], an early step in the formation of gastric carcinomas [6]. Nup88 is over expressed in ovarian cancer [13], lymphomas, mesotheliomas, a broad spectrum of sarcomas and in some epithelial cancers [14] In breast, colorectal and hepatocellular carcinoma Nup88 over expression is associated with tumor aggressiveness [15]. "
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    ABSTRACT: The intracellular location and regulation of proteins within each cell is critically important and is typically deregulated in disease especially cancer. The clinical hypothesis for inhibiting the nucleo-cytoplasmic transport is based on the dependence of certain key proteins within malignant cells. This includes a host of well-characterized tumor suppressor and oncoproteins that require specific localization for their function. This aberrant localization of tumour suppressors and oncoproteins results in their their respective inactivation or over-activation. This incorrect localization occurs actively via the nuclear pore complex that spans the nuclear envelope and is mediated by transport receptors. Accordingly, given the significant need for novel, specific disease treatments, the nuclear envelope and the nuclear transport machinery have emerged as a rational therapeutic target in oncology to restore physiological nucleus/cytoplasmic homeostasis. Recent evidence suggests that this approach might be of substantial therapeutic use. This review summarizes the mechanisms of nucleo-cytoplasmic transport, its role in cancer biology and the therapeutic potential of targeting this critical cellular process.
    Full-text · Article · Nov 2013 · Oncotarget
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