ArticleNeoplasia (New York, N.Y.)2018
Inhibition of mTORC2/RICTOR Impairs Melanoma Hepatic Metastasis.
Article in Neoplasia (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 47 citations in OpenAlex.
- Unveiling the Role of Mechanistic Target of Rapamycin Kinase (MTOR) Signaling in Cancer Progression and the Emergence of MTOR Inhibitors as Therapeutic Strategies.ACS pharmacology & translational science · 2024Review
- Review
- RICTOR/mTORC2 downregulation in BRAFMolecular cancer · 2024Article
- Review
- Article
- mTOR hyperactivity andPathology oncology research : POR · 2024Review
- Loss of Macrophage mTORC2 Drives Atherosclerosis via FoxO1 and IL-1β Signaling.Circulation research · 2023Article
- Role of Fibroblast Growth Factors in the Crosstalk of Hepatic Stellate Cells and Uveal Melanoma Cells in the Liver Metastatic Niche.International journal of molecular sciences · 2022Article
- mTOR Signaling Components in Tumor Mechanobiology.International journal of molecular sciences · 2022Review
- Predominant Role of mTOR Signaling in Skin Diseases with Therapeutic Potential.International journal of molecular sciences · 2022Review
- Role of mammalian target of rapamycin complex 2 in primary and secondary liver cancer.World journal of gastrointestinal oncology · 2021Review
- Article
- Autophagy and the Lysosomal System in Cancer.Cells · 2021Review
- Cancer-associated cells release citrate to support tumour metastatic progression.Life science alliance · 2021Article
- Dual Inhibition of mTORC1/2 Reduces Migration of Cholangiocarcinoma Cells by Regulation of Matrixmetalloproteinases.Frontiers in cell and developmental biology · 2021Article
- Pharmacological Inhibition of mTORC2 Reduces Migration and Metastasis in Melanoma.International journal of molecular sciences · 2020Article
- Development and optimization of orthotopic liver metastasis xenograft mouse models in uveal melanoma.Journal of translational medicine · 2020Article
- mTOR at the nexus of nutrition, growth, ageing and disease.Nature reviews. Molecular cell biology · 2020Review
- Review
- Identification of Novel Fusion Transcripts in Undifferentiated Pleomorphic Sarcomas by Transcriptome Sequencing.Cancer genomics & proteomicsArticle
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian target of rapamycin complex 2 (mTORC2) with its pivotal component rapamycin-insensitive companion of mTOR (RICTOR) is the major regulator of AKT phosphorylation and is increasingly implicated in tumor growth and progression. In cutaneous melanoma, an extremely aggressive and highly metastatic disease, RICTOR overexpression is involved in tumor development and invasiveness. Therefore, we investigated the impact of RICTOR inhibition in melanoma cells in vitro and in vivo with special emphasis on hepatic metastasis. Moreover, our study focused on the interaction of tumor cells and hepatic stellate cells (HSC) which play a crucial role in the hepatic microenvironment. In silico analysis revealed increased RICTOR expression in melanoma cells and tissues and indicated higher expression in advanced melanoma stages and metastases. In vitro, transient RICTOR knock-down via siRNA caused a significant reduction of tumor cell motility. Using a syngeneic murine splenic injection model, a significant decrease in liver metastasis burden was detected in vivo. Moreover, stimulation of melanoma cells with conditioned medium (CM) from activated HSC or hepatocyte growth factor (HGF) led to a significant induction of AKT phosphorylation and tumor cell motility. Blocking of RICTOR expression in cancer cells diminished constitutive and HGF-induced AKT phosphorylation as well as cell motility. Interestingly, RICTOR blockade also led to an abrogation of CM-induced effects on AKT phosphorylation and motility in melanoma cells. In conclusion, these results provide first evidence for a critical role of mTORC2/RICTOR in melanoma liver metastasis via cancer cell/HSC interactions.
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