Evidence map›Paper›PMID 28696138›Full record

ArticleAutophagy2017

ADIPOQ/adiponectin induces cytotoxic autophagy in breast cancer cells through STK11/LKB1-mediated activation of the AMPK-ULK1 axis.

Seung J Chung, Ganji Purnachandra Nagaraju, Arumugam Nagalingam, Nethaji Muniraj, Panjamurthy Kuppusamy, Alyssa Walker, Juhyung Woo, Balázs Győrffy, Ed Gabrielson, Neeraj K Saxena and 1 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Autophagy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed, 3 pooled it
10.2field-weighted citation impact, top 1% 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

134 citing papers in PubMed, 3 syntheses or guidelines pooled it, 222 citations in OpenAlex.

  1. Pooled it
  2. Genetic alterations inFrontiers in oncology · 2023
    Pooled it
  3. Guideline
  4. Review
  5. Article
  6. Cancers · 2026
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Article

74 more citing papers are in PubMed but not listed here.

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

11 authors at 5 institutions in 2 countries.

Seung J Chunga Department of Oncology , Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins , Baltimore , MD , USA.
Ganji Purnachandra Nagarajub Winship Cancer Institute , Emory University , Atlanta , GA , USA.
Arumugam Nagalingama Department of Oncology , Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins , Baltimore , MD , USA.
Nethaji Muniraja Department of Oncology , Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins , Baltimore , MD , USA.
Panjamurthy Kuppusamyc Department of Medicine , University of Maryland School of Medicine , Baltimore , MD , USA.
Alyssa Walkera Department of Oncology , Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins , Baltimore , MD , USA.
Juhyung Wooa Department of Oncology , Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins , Baltimore , MD , USA.
Balázs Győrffyd MTA TTK Momentum Cancer Biomarker Research Group , Budapest , Hungary.
Ed Gabrielsona Department of Oncology , Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins , Baltimore , MD , USA.
Neeraj K Saxenac Department of Medicine , University of Maryland School of Medicine , Baltimore , MD , USA.
Dipali Sharmaa Department of Oncology , Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins , Baltimore , MD , USA.
Sidney Kimmel Comprehensive Cancer Center · USJohns Hopkins University · USUniversity of Maryland, Baltimore · USEmory University · USSemmelweis University · HU

Funding

Inhibition of leptin-signaling axis in breast cancer by BITCR21CA155686 · NCI · JOHNS HOPKINS UNIVERSITY · PI SHARMA, DIPALI · 2014 to 2015
$388k
NCI NIH HHS R21 CA155686
6 · The paper itself

Abstract

ADIPOQ/adiponectin, an adipocytokine secreted by adipocytes in the breast tumor microenvironment, negatively regulates cancer cell growth hence increased levels of ADIPOQ/adiponectin are associated with decreased breast cancer growth. However, its mechanisms of action remain largely elusive. We report that ADIPOQ/adiponectin induces a robust accumulation of autophagosomes, increases MAP1LC3B-II/LC3B-II and decreases SQSTM1/p62 in breast cancer cells. ADIPOQ/adiponectin-treated cells and xenografts exhibit increased expression of autophagy-related proteins. LysoTracker Red-staining and tandem-mCherry-GFP-LC3B assay show that fusion of autophagosomes and lysosomes is augmented upon ADIPOQ/adiponectin treatment. ADIPOQ/adiponectin significantly inhibits breast cancer growth and induces apoptosis both in vitro and in vivo, and these events are preceded by macroautophagy/autophagy, which is integral for ADIPOQ/adiponectin-mediated cell death. Accordingly, blunting autophagosome formation, blocking autophagosome-lysosome fusion or genetic-knockout of BECN1/Beclin1 and ATG7 effectively impedes ADIPOQ/adiponectin induced growth-inhibition and apoptosis-induction. Mechanistic studies show that ADIPOQ/adiponectin reduces intracellular ATP levels and increases PRKAA1 phosphorylation leading to ULK1 activation. AMPK-inhibition abrogates ADIPOQ/adiponectin-induced ULK1-activation, LC3B-turnover and SQSTM1/p62-degradation while AMPK-activation potentiates ADIPOQ/adiponectin's effects. Further, ADIPOQ/adiponectin-mediated AMPK-activation and autophagy-induction are regulated by upstream master-kinase STK11/LKB1, which is a key node in antitumor function of ADIPOQ/adiponectin as STK11/LKB1-knockout abrogates ADIPOQ/adiponectin-mediated inhibition of breast tumorigenesis and molecular analyses of tumors corroborate in vitro mechanistic findings. ADIPOQ/adiponectin increases the efficacy of chemotherapeutic agents. Notably, high expression of ADIPOQ receptor ADIPOR2, ADIPOQ/adiponectin and BECN1 significantly correlates with increased overall survival in chemotherapy-treated breast cancer patients. Collectively, these data uncover that ADIPOQ/adiponectin induces autophagic cell death in breast cancer and provide in vitro and in vivo evidence for the integral role of STK11/LKB1-AMPK-ULK1 axis in ADIPOQ/adiponectin-mediated cytotoxic autophagy.

Indexed as

AdiponectinAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsAntineoplastic AgentsApoptosisAutophagosomesAutophagyAutophagy-Related Protein-1 HomologBeclin-1BiomarkersBreast NeoplasmsCell Line, TumorCell ProliferationCell SurvivalEnergy MetabolismAdiponectinAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAntineoplastic AgentsAutophagy-Related Protein-1 HomologBeclin-1BECN1 protein, humanBiomarkersIntracellular Signaling Peptides and ProteinsProtein Serine-Threonine KinasesSTK11 protein, humanULK1 protein, humanadiponectinAMPKautophagybreast cancerSTK11/LKB1ULK1

Identifiers

PMID28696138
PMCPMC5584870
OpenAlexW2734329550

What OpenQuestion holds

Textmetadata
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.