Evidence map›Paper›PMID 24556693›Full record

ArticleCell death & disease2014

Phosphorylated AKT inhibits the apoptosis induced by DRAM-mediated mitophagy in hepatocellular carcinoma by preventing the translocation of DRAM to mitochondria.

K Liu, Y Shi, X H Guo, Y B Ouyang, S S Wang, D J Liu, A N Wang, N Li, D X Chen

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

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

26 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. The p53 target DRAM1 modulates calcium homeostasis and ER stress by promoting contact between lysosomes and the ER through STIM1.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

9 authors at 3 institutions in 1 country.

K Liu1] Beijing Institute of Hepatology, Beijing, China [2] Beijing You'an Hospital, Capital Medical University, Beijing, China.
Y Shi1] Beijing Institute of Hepatology, Beijing, China [2] Beijing You'an Hospital, Capital Medical University, Beijing, China.
X H Guo1] Beijing Institute of Hepatology, Beijing, China [2] Beijing You'an Hospital, Capital Medical University, Beijing, China.
Y B Ouyang1] Beijing Institute of Hepatology, Beijing, China [2] Beijing You'an Hospital, Capital Medical University, Beijing, China.
S S Wang1] Beijing Institute of Hepatology, Beijing, China [2] Beijing You'an Hospital, Capital Medical University, Beijing, China.
D J Liu1] Beijing Institute of Hepatology, Beijing, China [2] Beijing You'an Hospital, Capital Medical University, Beijing, China.
A N Wang1] Beijing Institute of Hepatology, Beijing, China [2] Beijing You'an Hospital, Capital Medical University, Beijing, China.
N LiBeijing You'an Hospital, Capital Medical University, Beijing, China.
D X ChenBeijing Institute of Hepatology, Beijing, China.
Beijing Institute of Neurosurgery · CNBeijing YouAn Hospital · CNCapital Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Increasing autophagy is beneficial for curing hepatocellular carcinoma (HCC). Damage-regulated autophagy modulator (DRAM) was recently reported to induce apoptosis by mediating autophagy. However, the effects of DRAM-mediated autophagy on apoptosis in HCC cells remain unclear. In this study, normal hepatocytes (7702) and HCC cell lines (HepG2, Hep3B and Huh7) were starved for 48 h. Starvation induced apoptosis and autophagy in all cell lines. We determined that starvation also induced DRAM expression and DRAM-mediated autophagy in both normal hepatocytes and HCC cells. However, DRAM-mediated autophagy was involved in apoptosis in normal hepatocytes but not in HCC cells, suggesting that DRAM-mediated autophagy fails to induce apoptosis in hepatoma in response to starvation. Immunoblot and immunofluorescence assays demonstrated that DRAM translocated to mitochondria and induced mitophagy, which led to apoptosis in 7702 cells. In HCC cells, starvation also activated the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, which blocks the translocation of DRAM to mitochondria through the binding of p-AKT to DRAM in the cytoplasm. Inactivation of the PI3K/AKT pathway rescued DRAM translocation to mitochondria; subsequently, mitochondrial DRAM induced apoptosis in HCC cells by mediating mitophagy. Our findings open new avenues for the investigation of the mechanisms of DRAM-mediated autophagy and suggest that promoting DRAM-mediated autophagy together with PI3K/AKT inhibition might be more effective for autophagy-based therapy in hepatoma.

Indexed as

AutophagyMitophagyApoptosisCarcinoma, HepatocellularDNA-Binding ProteinsEnzyme ActivationHep G2 CellsHumansLiver NeoplasmsMembrane ProteinsMitochondriaNuclear ProteinsPhosphorylationProtein Kinase InhibitorsProtein TransportProto-Oncogene Proteins c-aktDNA-Binding ProteinsDRAM1 protein, humanMembrane ProteinsNuclear ProteinsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktTP53 protein, humanTumor Protein p73Tumor Suppressor Protein p53Tumor Suppressor Proteins

Identifiers

PMID24556693
PMCPMC3944266
OpenAlexW2065300578

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.