ArticleMolecular cell2016
Inhibition of Rb Phosphorylation Leads to mTORC2-Mediated Activation of Akt.
Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Pooled it
- mTORC1/2 inhibition induces tumor regression in CDK4/6 inhibitor-insensitive acral melanoma.Cancer gene therapy · 2026Article
- Article
- Clear cell renal carcinoma essentially requires CDKL3 for oncogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Review
- Combined inhibition of CDK4/6 and AKT is highly effective against the luminal androgen receptor (LAR) subtype of triple negative breast cancer.Cancer letters · 2024Article
- 56Fe-ion Exposure Increases the Incidence of Lung and Brain Tumors at a Similar Rate in Male and Female Mice.Radiation research · 2024Article
- Retinoblastoma-associated protein is important for TRIM24-mediated activation of the mTOR signaling pathway through DUSP2 action in prostate cancer.Cell death and differentiation · 2024Article
- Patterns in the tapestry of chromatin-bound RB.Trends in cell biology · 2024Review
- Integrative modeling uncovers p21-driven drug resistance and prioritizes therapies for PIK3CA-mutant breast cancer.NPJ precision oncology · 2024Article
- Review
- Unmasking the tumourigenic role of SIN1/MAPKAP1 in the mTOR complex 2.Clinical and translational medicine · 2023Review
- Real-World Evaluation of Disease Progression After CDK 4/6 Inhibitor Therapy in Patients With Hormone Receptor-Positive Metastatic Breast Cancer.The oncologist · 2023Article
- Investigation of the Therapeutic Effects of Palbociclib Conjugated Magnetic Nanoparticles on Different Types of Breast Cancer Cell Lines.Cellular and molecular bioengineering · 2023Article
- Prognostic Relevance and In Vitro Targeting of Concomitant PTEN and p16 Deficiency in Chordomas.Cancers · 2023Article
- Targeting mTOR to overcome resistance to hormone and CDK4/6 inhibitors in ER-positive breast cancer models.Scientific reports · 2023Article
- Combined inhibition of ACLY and CDK4/6 reduces cancer cell growth and invasion.Oncology reports · 2023Article
- miR-199a-3p increases the anti-tumor activity of palbociclib in liver cancer models.Molecular therapy. Nucleic acids · 2022Article
- Post-translational modifications on the retinoblastoma protein.Journal of biomedical science · 2022Review
- Targeting CDK4 and CDK6 in cancer.Nature reviews. Cancer · 2022Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
The retinoblastoma (Rb) protein exerts its tumor suppressor function primarily by inhibiting the E2F family of transcription factors that govern cell-cycle progression. However, it remains largely elusive whether the hyper-phosphorylated, non-E2F1-interacting form of Rb has any physiological role. Here we report that hyper-phosphorylated Rb directly binds to and suppresses the function of mTORC2 but not mTORC1. Mechanistically, Rb, but not p107 or p130, interacts with Sin1 and blocks the access of Akt to mTORC2, leading to attenuated Akt activation and increased sensitivity to chemotherapeutic drugs. As such, inhibition of Rb phosphorylation by depleting cyclin D or using CDK4/6 inhibitors releases Rb-mediated mTORC2 suppression. This, in turn, leads to elevated Akt activation to confer resistance to chemotherapeutic drugs in Rb-proficient cells, which can be attenuated with Akt inhibitors. Therefore, our work provides a molecular basis for the synergistic usage of CDK4/6 and Akt inhibitors in treating Rb-proficient cancer.
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Registered trials
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.