Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB

Douma, Sirith; Laar, Theo van; Zevenhoven, John; Meuwissen, Roger; Garderen, E. van; Peeper, Daniel S.

doi:10.1038/nature02765

Cited by 541 publications

(503 citation statements)

References 27 publications

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“…In addition, the tropomyosin-related kinase B (TrkB), whose over-expression has been documented in several tumours [125][126][127], is a potent and specific suppressor of anoikis [128]. Transfection of TrkB in highly anoikis-sensitive rat intestinal epithelial cells confers anoikis resistance through the activation of the PI3K-Akt pathway [128].…”

Section: Taddei Et Almentioning

confidence: 99%

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Anoikis: an emerging hallmark in health and diseases

Taddei

Giannoni

Fiaschi

et al. 2011

The Journal of Pathology

524

404

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Anoikis is a programmed cell death occurring upon cell detachment from the correct extracellular matrix, thus disrupting integrin ligation. It is a critical mechanism in preventing dysplastic cell growth or attachment to an inappropriate matrix. Anoikis prevents detached epithelial cells from colonizing elsewhere and is thus essential for tissue homeostasis and development. As anchorage-independent growth and epithelial-mesenchymal transition, two features associated with anoikis resistance, are crucial steps during tumour progression and metastatic spreading of cancer cells, anoikis deregulation has now evoked particular attention from the scientific community. The aim of this review is to analyse the molecular mechanisms governing both anoikis and anoikis resistance, focusing on their regulation in physiological processes, as well as in several diseases, including metastatic cancers, cardiovascular diseases and diabetes.

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Section: Taddei Et Almentioning

confidence: 99%

“…Transfection of TrkB in highly anoikis-sensitive rat intestinal epithelial cells confers anoikis resistance through the activation of the PI3K-Akt pathway [128]. Furthermore, TrkB over-expression results in EMT via the induction of Twist and Snail [129].…”

Section: Taddei Et Almentioning

confidence: 99%

Anoikis: an emerging hallmark in health and diseases

Taddei

Giannoni

Fiaschi

et al. 2011

The Journal of Pathology

524

404

View full text Add to dashboard Cite

show abstract

“…18 In addition, there may be a role for small molecule inhibitors in other cancer settings; for example, TRKB has been reported as a strong predictor of aggressive tumor growth in neuroblastoma, and it is also associated with increase resistance to chemotherapy and anoikis. 19,20 Moreover, high and increased expression of TRK receptors in pancreatic cancer correlates to tumor progression, perineural invasion, pain, and metastasis. 7,21−23 Several very potent nonselective TRK inhibitors have been described, and some of them have entered the clinic.…”

mentioning

confidence: 99%

Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models

Albaugh

Fan

et al. 2012

ACS Med. Chem. Lett.

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Neurotrophins and their receptors (TRKs) play key roles in the development of the nervous system and the maintenance of the neural network. Accumulating evidence points to their role in malignant transformations, chemotaxis, metastasis, and survival signaling and may contribute to the pathogenesis of a variety of tumors of both neural and non-neural origin. By screening the GNF kinase collection, a series of novel oxindole inhibitors of TRKs were identified. Optimization led to the identification of GNF-5837 (22), a potent, selective, and orally bioavailable pan-TRK inhibitor that inhibited tumor growth in a mouse xenograft model derived from RIE cells expressing both TRKA and NGF. The properties of 22 make it a good tool for the elucidation of TRK biology in cancer and other nononcology indications.

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Section: Introductionmentioning

confidence: 99%

“…Cell viability under anchorage-dependent conditions is regulated by integrin signal transduction through its interaction with the extracellular matrix. Various oncogenes expressed in transformed and cancer cells cause constitutive activation of the integrin signaling pathway which results in anoikis resistance [2,3].In our screening program of new antitumor compounds from microbial secondary metabolites, anicemycin (Fig. 1) was isolated as an inhibitor of anchorage-independent growth from Streptomyces sp.…”

mentioning

confidence: 99%

Anicemycin, a New Inhibitor of Anchorage-independent Growth of Tumor Cells from Streptomyces sp. TP-A0648

et al. 2005

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The anchorage-independence of cells is closely related to their tumorigenicity. In the screening of inhibitors of anchorage-independent growth of tumor cells, anicemycin was isolated from the fermentation broth of an actinomycete strain TP-A0648. The producing strain was isolated from a leaf of Aucuba japonica collected in Toyama, Japan and identified as Streptomyces sp. based on the taxonomic data. The structure of anicemycin was elucidated as a new analog of spicamycin by NMR and MS analysis. Anicemycin inhibited the anchorage-independent growth of the human ovary cancer SKOV-3 cells with an IC 50 of 0.015 mM about three times more potently than their anchorage-dependent growth.Keywords anicemycin, anchorage-independent growth, cytotoxic, spicamycin, Streptomyces IntroductionMost of the previously developed antitumor agents act mainly on the nucleic acid biosynthesis, DNA or microtubules and therefore these agents show cytotoxicity to normal tissues with significant adverse effects. Recent researches on the mechanism of cancer have been disclosing that a number of oncogenes are involved in tumorigenesis and many of these gene products are functioning as signal transduction molecules. The agents that inhibit the signal transduction of oncogenes are expected to become selective and safe anticancer drugs [1].The normal cells derived from epithelial and endothelial cells can proliferate only when they attach to the firm substrate. When these cells detach from the substrate and lose contact with the matrix, they die in an apoptotic process termed 'anoikis'. On the other hand, cancer cells usually have developed resistance to anoikis and show growth ability without the firm substrate attachment, namely the anchorage-independence. Cell viability under anchorage-dependent conditions is regulated by integrin signal transduction through its interaction with the extracellular matrix. Various oncogenes expressed in transformed and cancer cells cause constitutive activation of the integrin signaling pathway which results in anoikis resistance [2,3].In our screening program of new antitumor compounds from microbial secondary metabolites, anicemycin (Fig. 1) was isolated as an inhibitor of anchorage-independent growth from Streptomyces sp. TP-A0648. In this paper, we describe the fermentation, isolation, structure and biological activity of anicemycin. Materials and Methods General Experimental ProceduresNMR experiments were performed on a JEOL JNM-LA400 NMR spectrometer. The MS spectra were measured on a JEOL JMS-HX110A spectrometer. UV spectra were

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Suppression of anoikis and induction of metastasis by the neurotrophic receptor TrkB

Cited by 541 publications

References 27 publications

Anoikis: an emerging hallmark in health and diseases

Anoikis: an emerging hallmark in health and diseases

Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models

Anicemycin, a New Inhibitor of Anchorage-independent Growth of Tumor Cells from Streptomyces sp. TP-A0648

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