ArticleJournal of cellular and molecular medicine2017
Dual inhibition of BDNF/TrkB and autophagy: a promising therapeutic approach for colorectal cancer.
Article in Journal of cellular and molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Neuro-immune interactions in gastrointestinal oncology: Mechanisms, challenges, and therapeutic potential.Innovation (Cambridge (Mass.)) · 2026Review
- Decoding autophagy in neuro-tumor crosstalk: from underlying mechanisms to translational opportunities.Theranostics · 2026Review
- Peripheral nerve remodeling in the tumor microenvironment: neuro-immune crosstalk, molecular mechanisms, and precision therapeutic.Frontiers in immunology · 2026Review
- Inactivation of necroptosis-promoting protein MLKL creates a therapeutic vulnerability in colorectal cancer cells.Cell death & disease · 2025Article
- Novel CAR-T cells targeting TRKB for the treatment of solid cancer.Apoptosis : an international journal on programmed cell death · 2024Article
- High NTRK2 protein expression levels may be associated with poorer prognosis of breast cancer patients.The Journal of international medical research · 2024Article
- Article
- Perineural invasion in colorectal cancer: mechanisms of action and clinical relevance.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- The nerve cells in gastrointestinal cancers: from molecular mechanisms to clinical intervention.Oncogene · 2024Review
- Chloroquine Induces ROS-mediated Macrophage Migration Inhibitory Factor Secretion and Epithelial to Mesenchymal Transition in ER-positive Breast Cancer Cell Lines.Journal of mammary gland biology and neoplasia · 2021Article
- Novel Methylation Biomarkers for Colorectal Cancer Prognosis.Biomolecules · 2021Review
- Autophagy and Extracellular Vesicles in Colorectal Cancer: Interactions and Common Actors?Cancers · 2021Review
- Overexpression of sortilin is associated with 5-FU resistance and poor prognosis in colorectal cancer.Journal of cellular and molecular medicine · 2021Article
- Multiplex coherent anti-Stokes Raman scattering microspectroscopy detection of lipid droplets in cancer cells expressing TrkB.Scientific reports · 2020Article
- The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management.International journal of molecular sciences · 2020Review
- Colorectal Cancer Invasion and Atrophy of the Enteric Nervous System: Potential Feedback and Impact on Cancer Progression.International journal of molecular sciences · 2020Review
- Neurotrophins and their involvement in digestive cancers.Cell death & disease · 2019Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) is the most common digestive cancer in the Western world. Despite effective therapies, resistance and/or recurrence frequently occur. The present study investigated the impact of two survival pathways-neurotrophic factors (TrkB/BDNF) and autophagy-on cell fate and tumour evolution. In vitro 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-siRNA overactivated TrkB/BDNF signaling. In vitro, dual inhibition improved the effectiveness of single treatment by significantly reducing metabolic activity and enhancing apoptotic cell death. These findings were accentuated in vivo, in which dual inhibition induced a spectacular reduction in tumour volume following long-term treatment (21 days for K252a and 12 days for CQ). Finally, significant amounts of phospho-TrkB and LC3II were found in the patients' 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.