ArticleOncogene2019
Inhibition of mTOR complex 1/p70 S6 kinase signaling elevates PD-L1 levels in human cancer cells through enhancing protein stabilization accompanied with enhanced β-TrCP degradation.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 84 citations in OpenAlex.
- Repurposed ethoxzolamide reprograms antitumor immunity through β-TrCP-dependent PD-L1 ubiquitination.Cell reports. Medicine · 2026Article
- TP53 Loss Fuels mTORC1 Activation and Autophagy Suppression to Drive Immune-Cold Colorectal Cancer.World journal of oncology · 2026Article
- Intracellular Localization of PD-L1 in Rab10-positive Open Tubular Endosome System of Cancer Cells.Acta histochemica et cytochemica · 2026Article
- Calorie Restriction Upregulates Islet PD-L1 Signaling and Decreases the Risk of Autoimmune Diabetes Onset in NOD Mice.bioRxiv : the preprint server for biology · 2026Article
- PI3K/AKT/mTOR signaling at the immune checkpoint interface in lung cancer: molecular mechanisms, Tumor-Immune remodeling, therapeutic resistance, and emerging treatment strategies.Frontiers in cell and developmental biology · 2026Review
- Programmed Death-1 Ligand 1 Domain Organization, Signaling Motifs, and Interactors in Cancer Immunotherapy.Cancers · 2025Review
- Post-translational modifications of immune checkpoints: unlocking new potentials in cancer immunotherapy.Experimental hematology & oncology · 2025Review
- Cholesterol suppresses AMFR-mediated PDL1 ubiquitination and degradation in HCC.Molecular and cellular biochemistry · 2025Article
- Ubiquitination Enzymes in Cancer, Cancer Immune Evasion, and Potential Therapeutic Opportunities.Cells · 2025Review
- Identify and validate a novel ubiquitination-related biomarker for thyroid cancer prognosis and immunotherapy.Frontiers in oncology · 2025Article
- Impact of Neoadjuvant Therapy on PD-L1 Expression in Triple-Negative Breast Cancer and Correlation with Clinicopathological Factors.Diagnostics (Basel, Switzerland) · 2024Article
- FAT10 induces immune suppression by upregulating PD-L1 expression in hepatocellular carcinoma.Apoptosis : an international journal on programmed cell death · 2024Article
- Article
- Regulation of post-translational modification of PD-L1 and associated opportunities for novel small-molecule therapeutics.Future medicinal chemistry · 2024Review
- Emerging Targets and Therapeutics in Immuno-Oncology: Insights from Landscape Analysis.Journal of medicinal chemistry · 2024Review
- Secondary metabolites of mulberry leaves exert anti-lung cancer activity through regulating the PD-L1/PD-1 signaling pathway.Journal of pharmaceutical analysis · 2024Article
- Inhibition of CK2/ING4 Pathway Facilitates Non-Small Cell Lung Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Hsa-LINC02418/mmu-4930573I07Rik regulated by METTL3 dictates anti-PD-L1 immunotherapeutic efficacy via enhancement of Trim21-mediated PD-L1 ubiquitination.Journal for immunotherapy of cancer · 2023Article
- Integrative multi-omics analysis unveils stemness-associated molecular subtypes in prostate cancer and pan-cancer: prognostic and therapeutic significance.Journal of translational medicine · 2023Article
- Autophagy as a Target for Non-Immune Intrinsic Functions of Programmed Cell Death-Ligand 1 in Cancer.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The involvement of mammalian target of rapamycin (mTOR) in the positive regulation of oncogenesis has been well documented and thus mTOR has emerged as an attractive cancer therapeutic target. Although rapamycin and its analogues (rapalogs) are FDA-approved for the treatment of certain cancers, major success in targeting mTOR, particularly with new generation mTOR kinase inhibitors, for the effective treatment of cancers has not been achieved. Hence, a thorough understanding of the biology of the mTOR axis in cancer is still needed. It is now recognized that programmed death-ligand 1 (PD-L1) expression on cancer cells is a critical mechanism contributing to immunosuppression and immune escape via interacting with program death-1 (PD-1) on immune cells. This study has revealed a previously undiscovered role of the mTOR complex 1 (mTORC1)/p70 S6 kinase (p70S6K) in the negative regulation of PD-L1 on cancer cells and tissues. We demonstrate that disruption of this signaling pathway with mTOR inhibitors, raptor knockdown or p70S6K inhibitors elevated PD-L1 levels in some lung and other cancer cell lines. Elevation of PD-L1 by inhibition of mTORC1/p70S6K signaling is likely due to suppression of β-TrCP-mediated proteasomal degradation of PD-L1, because inhibition of either mTORC1 or p70S6K facilitated β-TrCP degradation accompanied with enhanced PD-L1 protein stabilization. Our current findings indicate the complexity of the mTOR axis in cancer, which should be considered when targeting this axis for effective cancer treatment. Our findings also suggest a strong scientific rationale for enhancing PD-1/PD-L1-targeted cancer immunotherapy through co-targeting mTORC1/p70S6K signaling.
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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.