ArticleOncotarget2017
Inhibition of mTORC2 component RICTOR impairs tumor growth in pancreatic cancer models.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
- Targeting KRAS-mutant pancreatic cancer through simultaneous inhibition of KRAS, MEK, and JAK2.Molecular oncology · 2025Article
- 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
- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
- mTOR hyperactivity andPathology oncology research : POR · 2024Review
- Novel RICTOR amplification harbouring entities: FISH validation of RICTOR amplification in tumour tissue after next-generation sequencing.Scientific reports · 2023Article
- SFPQ and Its Isoform as Potential Biomarker for Non-Small-Cell Lung Cancer.International journal of molecular sciences · 2023Article
- The role of metabolic ecosystem in cancer progression - metabolic plasticity and mTOR hyperactivity in tumor tissues.Cancer metastasis reviews · 2021Review
- Role of mammalian target of rapamycin complex 2 in primary and secondary liver cancer.World journal of gastrointestinal oncology · 2021Review
- Current and emerging therapeutic strategies in pancreatic cancer: Challenges and opportunities.World journal of gastroenterology · 2021Review
- Targeting KRAS in pancreatic cancer: new drugs on the horizon.Cancer metastasis reviews · 2021Review
- Emerging role of metabolic reprogramming in tumor immune evasion and immunotherapy.Science China. Life sciences · 2021Review
- 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
- Overcoming Adaptive Resistance to KRAS and MEK Inhibitors by Co-targeting mTORC1/2 Complexes in Pancreatic Cancer.Cell reports. Medicine · 2020Article
- RICTOR/mTORC2 affects tumorigenesis and therapeutic efficacy of mTOR inhibitors in esophageal squamous cell carcinoma.Acta pharmaceutica Sinica. B · 2020Article
- Regulation of stanniocalcin-1 secretion by BeWo cells and first trimester human placental tissue from normal pregnancies and those at increased risk of developing preeclampsia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- The role of RICTOR amplification in targeted therapy and drug resistance.Molecular medicine (Cambridge, Mass.) · 2020Review
- SGK1 in Human Cancer: Emerging Roles and Mechanisms.Frontiers in oncology · 2020Review
- Small nucleolar RNA host gene 1 promotes development and progression of colorectal cancer through negative regulation of miR-137.Molecular carcinogenesis · 2019Article
- mTORC2 deficiency in cutaneous dendritic cells potentiates CD8American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2019Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mammalian Target of Rapamycin complex 2 (mTORC2) and its regulatory component Rapamycin-insensitive companion of mTOR (RICTOR) are increasingly recognized as important players in human cancer development and progression. However, the role of RICTOR in human pancreatic ductal adenocarcinoma (PDAC) is unclear so far. Here, we sought to analyze the effects of RICTOR inhibition in human pancreatic cancer cell lines in vitro and in vivo. Furthermore, RICTOR expression was determined in human PDAC samples. Results demonstrate that depletion of RICTOR with siRNA (transient knock-down) or shRNA (stable knock-down) has an inhibitory effect on tumor growth in vitro. Moreover, RICTOR inhibition led to impaired phosphorylation/activity of AGC kinases (AKT, SGK1). Interestingly, hypoxia-induced expression of hypoxia-induced factor-1α (HIF-1α) was diminished and secretion of vascular-endothelial growth factor-A (VEGF-A) was impaired upon targeting RICTOR. Stable RICTOR knock-down led to significant inhibition of tumor growth in subcutaneous and orthotopic tumor models which was accompanied by significant reduction of tumor cell proliferation. Finally, immunohistochemical analyses of 85 human PDAC samples revealed significantly poorer survival in patients with higher RICTOR expression. In conclusion, these findings provide first evidence for mTORC2/RICTOR as an attractive novel target for treatment of human PDAC.
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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 Socratic graph.