ArticleCell death and differentiation2017
mTORC1-independent autophagy regulates receptor tyrosine kinase phosphorylation in colorectal cancer cells via an mTORC2-mediated mechanism.
Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 68 citations in OpenAlex.
- Attack cancer: Through autophagic modulations as suppressor or promoter.World journal of clinical oncology · 2025Review
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- NAT10 Knockdown Improves Cisplatin Sensitivity in Non-Small Cell Lung Cancer by Inhibiting the TRIM44/PI3K/AKT Pathway.Thoracic cancer · 2025Article
- An Update on the Study of the Molecular Mechanisms Involved in Autophagy during Bacterial Pathogenesis.Biomedicines · 2024Review
- Complex Interplay between DNA Damage and Autophagy in Disease and Therapy.Biomolecules · 2024Review
- Role of protein degradation systems in colorectal cancer.Cell death discovery · 2024Review
- USP10 suppresses ABCG2-induced malignant characteristics of doxorubicin-resistant thyroid cancer by inhibiting PI3K/AKT pathway.Journal of bioenergetics and biomembranes · 2023Article
- Autophagy and autophagy-related pathways in cancer.Nature reviews. Molecular cell biology · 2023Review
- Dysregulated Signalling Pathways Driving Anticancer Drug Resistance.International journal of molecular sciences · 2023Review
- Autophagy Induction byPharmaceuticals (Basel, Switzerland) · 2023Review
- Autophagy and the Insulin-like Growth Factor (IGF) System in Colonic Cells: Implications for Colorectal Neoplasia.International journal of molecular sciences · 2023Review
- Candidate genes potentially involved in molting and body size reduction in the male of the horned gall aphid,Frontiers in physiology · 2023Article
- Aberrant paracrine signalling for bone remodelling underlies the mutant histone-driven giant cell tumour of bone.Cell death and differentiation · 2022Article
- Autophagy Signaling by Neural-Induced Human Adipose Tissue-Derived Stem Cell-Conditioned Medium during Rotenone-Induced Toxicity in SH-SY5Y Cells.International journal of molecular sciences · 2022Article
- Dengue activates mTORC2 signaling to counteract apoptosis and maximize viral replication.Frontiers in cellular and infection microbiology · 2022Article
- Article
- Icariin alleviates osteoarthritis by regulating autophagy of chondrocytes by mediating PI3K/AKT/mTOR signaling.Bioengineered · 2021Article
- The role of metabolic ecosystem in cancer progression - metabolic plasticity and mTOR hyperactivity in tumor tissues.Cancer metastasis reviews · 2021Review
- mTORC2: The other mTOR in autophagy regulation.Aging cell · 2021Review
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6 authors at 3 institutions in 1 country.
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Abstract
The intracellular autophagic degradative pathway can have a tumour suppressive or tumour-promoting role depending on the stage of tumour development. Upon starvation or targeting of oncogenic receptor tyrosine kinases (RTKs), autophagy is activated owing to the inhibition of PI3K/AKT/mTORC1 signalling pathway and promotes survival, suggesting that autophagy is a relevant therapeutic target in these settings. However, the role of autophagy in cancer cells where the PI3K/AKT/mTORC1 pathway is constitutively active remains partially understood. Here we report a role for mTORC1-independent basal autophagy in regulation of RTK activation and cell migration in colorectal cancer (CRC) cells. PI3K and RAS-mutant CRC cells display basal autophagy levels despite constitutive mTORC1 signalling, but fail to increase autophagic flux upon RTK inhibition. Inhibition of basal autophagy via knockdown of ATG7 or ATG5 leads to decreased phosphorylation of several RTKs, in particular c-MET. Internalised c-MET colocalised with LAMP1-negative, LC3-positive vesicles. Finally, autophagy regulates c-MET phosphorylation via an mTORC2-dependent mechanism. Overall, our findings reveal a previously unappreciated role of autophagy and mTORC2 in regulation of oncogenic RTK activation, with implications for understanding of cancer cell signalling.
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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.