ArticleCancer research2020
Phosphorylation of RAB7 by TBK1/IKKε Regulates Innate Immune Signaling in Triple-Negative Breast Cancer.
Article in Cancer research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- Discovery of N8: a novel IKKε inhibitor with potent anticancer activity via cytotoxicity, migration suppression, and autophagy modulation.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Mitochondrial Fis1 tunes Rab7A activity via TBC1D15 modulating STING degradation.Cell reports · 2026Article
- Characterization of a transmembrane-activating STING agonist using genetically humanized mice.Cell reports · 2026Article
- Tumor-infiltrating lymphocytes in triple-negative breast cancer: molecular mechanisms, spatial regulation, and therapeutic implications.Breast cancer research : BCR · 2026Review
- TBK1 activity regulates the directionality of axonal transport of signalling endosomes.Life science alliance · 2026Article
- Microglial TBK1 Signaling Promotes Breast Cancer Brain Metastasis.Cancer research · 2026Article
- Macrophage TBK1 signaling drives the development and outgrowth of breast cancer brain metastasis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Molecular features of TNBC govern heterogeneity in the response to radiation and autophagy inhibition.Cell death & disease · 2025Article
- Immune targeting of triple-negative breast cancer through a clinically actionable STING agonist-CAR T cell platform.Cell reports. Medicine · 2025Article
- LMTK3 regulation of EV biogenesis and cargo sorting promotes tumour growth by reducing monocyte infiltration and driving pro-tumourigenic macrophage polarisation in breast cancer.Molecular cancer · 2025Article
- TBK1 and IKKε prevent premature cell death by limiting the activity of both RIPK1 and NLRP3 death pathways.Science advances · 2025Article
- Phosphorylation on serine 72 modulates Rab7A palmitoylation and retromer recruitment.Journal of cell science · 2025Article
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- TBK1-Zyxin signaling controls tumor-associated macrophage recruitment to mitigate antitumor immunity.The EMBO journal · 2024Article
- Human breast tissue engineering in health and disease.EMBO molecular medicine · 2024Review
- Lysosomal TBK1 responds to amino acid availability to relieve Rab7-dependent mTORC1 inhibition.The EMBO journal · 2024Article
- TREX1 Inactivation Unleashes Cancer Cell STING-Interferon Signaling and Promotes Antitumor Immunity.Cancer discovery · 2024Article
- Distinct early role of PTEN regulation during HCMV infection of monocytes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- FOXO3/Rab7-Mediated Lipophagy and Its Role in Zn-Induced Lipid Metabolism in Yellow Catfish (Genes · 2024Article
- TBK1 is paradoxical in tumor development: a focus on the pathway mediating IFN-I expression.Frontiers in immunology · 2024Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
Triple-negative breast cancer (TNBC) is a heterogeneous disease enriched for mutations in PTEN and dysregulation of innate immune signaling. Here, we demonstrate that Rab7, a recently identified substrate of PTEN phosphatase activity, is also a substrate of the innate immune signaling kinases TANK-binding kinase 1 (TBK1)/IκB kinase ε (IKKε) on the same serine-72 (S72) site. An unbiased search for novel TBK1/IKKε substrates using stable isotope labeling with amino acids in cell culture phosphoproteomic analysis identified Rab7-S72 as a top hit. PTEN-null TNBC cells expressing a phosphomimetic version of Rab7-S72 exhibited diffuse cytosolic Rab7 localization and enhanced innate immune signaling, in contrast to a kinase-resistant version, which localized to active puncta that promote lysosomal-mediated stimulator of interferon genes (STING) degradation. Thus, convergence of PTEN loss and TBK1/IKKε activation on Rab7-S72 phosphorylation limited STING turnover and increased downstream production of IRF3 targets including CXCL10, CCL5, and IFNβ. Consistent with this data, PTEN-null TNBC tumors expressed higher levels of STING, and PTEN-null TNBC cell lines were hyperresponsive to STING agonists. Together, these findings begin to uncover how innate immune signaling is dysregulated downstream of TBK1/IKKε in a subset of TNBCs and reveals previously unrecognized cross-talk with STING recycling that may have implications for STING agonism in the clinic. SIGNIFICANCE: These findings identify Rab7 as a substrate for TBK1 for regulation of innate immune signaling, thereby providing important insight for strategies aimed at manipulating the immune response to enhance therapeutic efficacy in TNBC.
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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.