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Pro-nerve growth factor induces autocrine stimulation of breast cancer cell invasion through tropomyosin-related kinase A (TrkA) and sortilin protein

Onglets principaux

Corbet, Cyril [UCL] Demont, Yohann Page, Adeline Ataman-Önal, Yasemin Choquet-Kastylevsky, Genevieve Hondermarck, Hubert

The precursor of nerve growth factor (proNGF) has been described as a biologically active polypeptide able to induce apoptosis in neuronal cells, via the neurotrophin receptor p75(NTR) and the sortilin receptor. Herein, it is shown that proNGF is produced and secreted by breast cancer cells, stimulating their invasion. Using Western blotting and mass spectrometry, proNGF was detected in a panel of breast cancer cells as well as in their conditioned media. Immunohistochemical analysis indicated an overproduction of proNGF in breast tumors, when compared with benign and normal breast biopsies, and a relationship to lymph node invasion in ductal carcinomas. Interestingly, siRNA against proNGF induced a decrease of breast cancer cell invasion that was restored by the addition of non-cleavable proNGF. The activation of TrkA, Akt, and Src, but not the MAP kinases, was observed. In addition, the proNGF invasive effect was inhibited by the Trk pharmacological inhibitor K252a, a kinase-dead TrkA, and siRNA against TrkA sortilin, neurotensin, whereas siRNA against p75(NTR) and the MAP kinase inhibitor PD98059 had no impact. These data reveal the existence of an autocrine loop stimulated by proNGF and mediated by TrkA and sortilin, with the activation of Akt and Src, for the stimulation of breast cancer cell invasion.

Type de document Article de périodique (Journal article) – Article de recherche
Type d'accès Accès interdit
Année de publication 2012
Langue Anglais
Information sur le périodique "Journal of Biological Chemistry" - Vol. 287, no. 3, p. 1923-1931 (2011)
Peer reviewed oui
Editeur American Society for Biochemistry and Molecular Biology, Inc.
issn 0021-9258
e-issn 1083-351X
Statut de la publication Publié
Affiliations UCL - SSS/IREC/FATH - Pôle de Pharmacologie et thérapeutique
MESH Subject Adaptor Proteins, Vesicular Transport ; Female ; Humans ; Indole Alkaloids ; Lymphatic Metastasis ; Neoplasm Invasiveness ; Nerve Growth Factor ; Protein Precursors ; Proto-Oncogene Proteins c-akt ; Receptor, trkA ; Receptors, Nerve Growth Factor ; Autocrine Communication ; src-Family Kinases ; Biopsy ; Breast Neoplasms ; Carbazoles ; Carcinoma, Ductal ; Cell Line, Tumor ; Enzyme Activation ; Enzyme Inhibitors
Liens
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Référence bibliographique Corbet, Cyril ; Demont, Yohann ; Page, Adeline ; Ataman-Önal, Yasemin ; Choquet-Kastylevsky, Genevieve ; et. al. Pro-nerve growth factor induces autocrine stimulation of breast cancer cell invasion through tropomyosin-related kinase A (TrkA) and sortilin protein. In: Journal of Biological Chemistry, Vol. 287, no. 3, p. 1923-1931 (2011)
Permalien http://hdl.handle.net/2078.1/158648