Evidence map›Paper›PMID 28933585›Full record

ArticleAutophagy2018

Oncogenic RAS-induced downregulation of ATG12 is required for survival of malignant intestinal epithelial cells.

Byong Hoon Yoo, Iman Aftab Khan, Ananda Koomson, Pramod Gowda, Takehiko Sasazuki, Senji Shirasawa, Shashi Gujar, Kirill V. Rosen

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

Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.7field-weighted citation impact, top 27% 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

14 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Therapeutic Effect and Mechanism of Cinnamyl Alcohol on Myocardial Ischemia-Reperfusion Injury.Evidence-based complementary and alternative medicine : eCAM · 2022
    Article
  10. Article
  11. Review
  12. Overexpression of the cohesin-core subunit SMC1A contributes to colorectal cancer development.Journal of experimental & clinical cancer research : CR · 2019
    Article
  13. Cell discovery · 2019
    Article
  14. 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

8 authors at 3 institutions in 2 countries.

Byong Hoon Yooa Departments of Pediatrics and Department of Biochemistry and Molecular Biology , Atlantic Research Centre, Dalhousie University , Halifax , NS , Canada.
Iman Aftab Khana Departments of Pediatrics and Department of Biochemistry and Molecular Biology , Atlantic Research Centre, Dalhousie University , Halifax , NS , Canada.
Ananda Koomsona Departments of Pediatrics and Department of Biochemistry and Molecular Biology , Atlantic Research Centre, Dalhousie University , Halifax , NS , Canada.
Pramod Gowdaa Departments of Pediatrics and Department of Biochemistry and Molecular Biology , Atlantic Research Centre, Dalhousie University , Halifax , NS , Canada.
Takehiko Sasazukib Institute for Advanced Study, Kyushu University , Fukuoka , Japan.
Senji Shirasawac Department of Cell Biology , Faculty of Medicine, and Center for Advanced Molecular Medicine, Fukuoka University , Fukuoka , Japan.
Shashi Gujard Department of Microbiology and Immunology , Dalhousie University , Halifax , NS , Canada.
Kirill V. Rosena Departments of Pediatrics and Department of Biochemistry and Molecular Biology , Atlantic Research Centre, Dalhousie University , Halifax , NS , Canada.
Dalhousie University · CAFukuoka University · JPKyushu University · JP

Funding

CIHR 125109
6 · The paper itself

Abstract

Activating mutations of RAS GTPase contribute to the progression of many cancers, including colorectal carcinoma. So far, attempts to develop treatments of mutant RAS-carrying cancers have been unsuccessful due to insufficient understanding of the salient mechanisms of RAS signaling. We found that RAS downregulates the protein ATG12 in colon cancer cells. ATG12 is a mediator of autophagy, a process of degradation and reutilization of cellular components. In addition, ATG12 can kill cells via autophagy-independent mechanisms. We established that RAS reduces ATG12 levels in cancer cells by accelerating its proteasomal degradation. We further observed that RAS-dependent ATG12 loss in these cells is mediated by protein kinases MAP2K/MEK and MAPK1/ERK2-MAPK3/ERK1, known effectors of RAS. We also demonstrated that the reversal of the effect of RAS on ATG12 achieved by the expression of exogenous ATG12 in cancer cells triggers both apoptotic and nonapoptotic signals and efficiently kills the cells. ATG12 is known to promote autophagy by forming covalent complexes with other autophagy mediators, such as ATG5. We found that the ability of ATG12 to kill oncogenic RAS-carrying malignant cells does not require covalent binding of ATG12 to other proteins. In summary, we have identified a novel mechanism by which oncogenic RAS promotes survival of malignant intestinal epithelial cells. This mechanism is driven by RAS-dependent loss of ATG12 in these cells.

Indexed as

AutophagyAnimalsApoptosisAutophagy-Related Protein 12Autophagy-Related Protein 5Cell Line, TumorCell SurvivalColorectal NeoplasmsDown-RegulationHumansIntestinal MucosaMAP Kinase Kinase KinasesMutationProtein BindingProto-Oncogene Proteins p21(ras)Signal TransductionATG12 protein, humanATG5 protein, humanAutophagy-Related Protein 12Autophagy-Related Protein 5KRAS protein, humanMAP Kinase Kinase KinasesProto-Oncogene Proteins p21(ras)apoptosisATG12autophagycolorectal cancerRAS

Identifiers

PMID28933585
PMCPMC5846558
OpenAlexW2760657482

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.