- Title
- Pro-nerve growth factor induces autocrine stimulation of breast cancer cell invasion through tropomyosin-related kinase A (TrkA) and sortilin protein
- Creator
- Demont, Yohann; Corbet, Cyril; Page, Adeline; Ataman-Önal, Yasemin; Choquet-Kastylevsky, Genevieve; Fliniaux, Ingrid; Le Bourhis, Xuefen; Toillon, Robert-Alain; Bradshaw, Ralph A.; Hondermarck, Hubert
- Relation
- Journal of Biological Chemistry Vol. 287, Issue 3, p. 1923-1931
- Publisher Link
- http://dx.doi.org/10.1074/jbc.M110.211714
- Publisher
- American Society for Biochemistry and Molecular Biology
- Resource Type
- journal article
- Date
- 2012
- Description
- 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 p75NTR 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 p75NTR 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.
- Subject
- breast cancer; cellular regulation; growth factors; neurotrophins; signal transduction; TrkA receptor; p75NTR
- Identifier
- http://hdl.handle.net/1959.13/1311592
- Identifier
- uon:22251
- Identifier
- ISSN:0021-9258
- Rights
- This research was originally published in Journal of Biological Chemistry. Demont, Yohann; Corbet, Cyril; Page, Adeline; Ataman-Onal, Yasemin; Choquet-Kastylevsky, Genevieve; Fliniaux, Ingrid; Le Bourhis, Xuefen; Toillon, Robert-Alain; Bradshaw, Ralph A.; Hondermarch, Hubert. Pro-nerve growth factor induces autocrine stimulation of breast cancer cell invasion through tropomyosin-related kinase A (TrkA) and sortilin protein. Journal of Biological Chemistry. 2012; Vol. 287, Issue 3: 1923-1931. © the American Society for Biochemistry and Molecular Biology. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/
- Language
- eng
- Full Text
- Reviewed
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