Evidence map›Paper›PMID 37733921›Full record

ArticleAutophagy2024

AZI2 mediates TBK1 activation at unresolved selective autophagy cargo receptor complexes with implications for CD8 T-cell infiltration in breast cancer.

Syn Kok Yeo, Michael Haas, Kanakaraju Manupati, Mingang Hao, Fuchun Yang, Song Chen, Jun-Lin Guan

Open access · hybridAbstract read
In one paragraph

Article in Autophagy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.3field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 8 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 2 countries.

Syn Kok YeoDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.ORCID 0000-0002-4333-2510
Michael HaasDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Kanakaraju ManupatiDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Mingang HaoDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Fuchun YangDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Song ChenDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Jun-Lin GuanDepartment of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
University of Cincinnati Medical Center · USZhengzhou University · CN

Funding

Mechanisms of progression of vascular malformation to lymphangiosarcomaR01HL073394 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GUAN, JUN-LIN · 2003 to 2025
$8.4M
Regulation of Neural Stem Cells and Neurogenesis by Autophagy GenesR01NS094144 · NINDS · UNIVERSITY OF CINCINNATI · PI GUAN, JUN-LIN · 2015 to 2024
$3.6M
Genetic Analysis of FAK kinase and scaffold functions in breast cancerR01CA163493 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI GUAN, JUN-LIN · 2012 to 2016
$1.6M
NCI NIH HHS R01 CA163493NHLBI NIH HHS R01 HL073394NINDS NIH HHS R01 NS094144
6 · The paper itself

Abstract

Most breast cancers do not respond to immune checkpoint inhibitors and there is an urgent need to identify novel sensitization strategies. Herein, we uncovered that activation of the TBK-IFN pathway that is mediated by the TBK1 adapter protein AZI2 is a potent strategy for this purpose. Our initial observations showed that RB1CC1 depletion leads to accumulation of AZI2, in puncta along with selective macroautophagy/autophagy cargo receptors, which are both required for TBK1 activation. Specifically, disrupting the selective autophagy function of RB1CC1 was sufficient to sustain AZI2 puncta accumulation and TBK1 activation. AZI2 then mediates downstream activation of DDX3X, increasing its interaction with IRF3 for transcription of pro-inflammatory chemokines. Consequently, we performed a screen to identify inhibitors that can induce the AZI2-TBK1 pathway, and this revealed Lys05 as a pharmacological agent that induced pro-inflammatory chemokine expression and CD8

Indexed as

Breast NeoplasmsMacroautophagyAutophagyCD8-Positive T-LymphocytesFemaleHumansProtein Serine-Threonine KinasesT-LymphocytesProtein Serine-Threonine KinasesTBK1 protein, humanAZI2breast cancerimmune checkpoint inhibitorRB1CC1TBK1

Identifiers

PMID37733921
PMCPMC10936636
OpenAlexW4386916383

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.