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The present study investigated the impact of two survival pathways\u2014neurotrophic factors (TrkB\/BDNF) and autophagy\u2014on cell fate and tumour evolution. <jats:italic>In vitro<\/jats:italic> studies were performed on two CRC cell lines, SW480 (primary tumour) and SW620 (lymph node invasion), which were also used for subcutaneous xenografts on a nude mouse model. In addition, the presence of neurotrophic factors (NTs) and autophagy markers were assessed in tissue samples representative of different stages. On the basis of our previous study (which demonstrated that TrkB overexpression is associated with prosurvival signaling in CRC cells), we pharmacologically inhibited NTs pathways with K252a. As expected, an inactivation of the PI3K\/AKT pathway was observed and CRC cells initiated autophagy. Conversely, blocking the autophagic flux with chloroquine or with ATG5\u2010siRNA overactivated TrkB\/BDNF signaling. <jats:italic>In vitro<\/jats:italic>, dual inhibition improved the effectiveness of single treatment by significantly reducing metabolic activity and enhancing apoptotic cell death. These findings were accentuated <jats:italic>in vivo,<\/jats:italic> in which dual inhibition induced a spectacular reduction in tumour volume following long\u2010term treatment (21 days for K252a and 12 days for CQ). Finally, significant amounts of phospho\u2010TrkB and LC3II were found in the patients\u2019 tissues, highlighting their relevance in CRC tumour biology. Taken together, our results show that targeting NTs and autophagy pathways potentially constitutes a new therapeutic approach for CRC.<\/jats:p>","DOI":"10.1111\/jcmm.13181","type":"journal-article","created":{"date-parts":[[2017,6,9]],"date-time":"2017-06-09T09:54:44Z","timestamp":1497002084000},"page":"2610-2622","source":"Crossref","is-referenced-by-count":30,"title":["Dual inhibition of BDNF\/TrkB and autophagy: a promising therapeutic approach for colorectal cancer"],"prefix":"10.1111","volume":"21","author":[{"given":"Cl\u00e9ment","family":"Mazouffre","sequence":"first","affiliation":[{"name":"Laboratoire EA 3842 Hom\u00e9ostasie cellulaire et Pathologies Facult\u00e9 de M\u00e9decine et de Pharmacie Universit\u00e9 de Limoges Limoges Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Geyl","sequence":"additional","affiliation":[{"name":"Laboratoire EA 3842 Hom\u00e9ostasie cellulaire et Pathologies Facult\u00e9 de M\u00e9decine et de 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