Evidence map›Paper›PMID 27503856›Full record

ArticleMolecular and cellular biology2016

Unravelling the Mechanism of TrkA-Induced Cell Death by Macropinocytosis in Medulloblastoma Daoy Cells.

Chunhui Li, James I S MacDonald, Asghar Talebian, Jennifer Leuenberger, Claudia Seah, Stephen H Pasternak, Stephen W Michnick, Susan O Meakin

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Macropinocytosis: mechanism and targeted therapy in cancers.American journal of cancer research · 2021
    Review
  5. Review
  6. Combined mTORC1/mTORC2 inhibition blocks growth and induces catastrophic macropinocytosis in cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  7. The pervasiveness of macropinocytosis in oncological malignancies.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019
    Review
  8. Article
  9. Article
  10. 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 2 institutions in 1 country.

Chunhui LiRobarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada.
James I S MacDonaldRobarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada.
Asghar TalebianDepartment of Biochemistry, Western University, London, Ontario, Canada.
Jennifer LeuenbergerDepartment of Biochemistry, Western University, London, Ontario, Canada.
Claudia SeahRobarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada.
Stephen H PasternakRobarts Research Institute, Schulich School of Medicine, Western University, London, Ontario, Canada Department of Clinical Neurological Sciences, Schulich School of Medicine, Western University, London, Ontario, Canada.
Stephen W MichnickDépartment de Biochimie, Université de Montreal, Montreal, Quebéc, Canada.
Susan O MeakinDepartment of Biochemistry, Western University, London, Ontario, Canada Graduate Program in Neuroscience, Western University, London, Ontario, Canada smeakin@uwo.ca.ORCID 0000-0003-2469-6615
Western University · CAUniversité de Montréal · CA

Funding

CIHR MOP-GMX-93643
6 · The paper itself

Abstract

Macropinocytosis is a normal cellular process by which cells internalize extracellular fluids and nutrients from their environment and is one strategy that Ras-transformed pancreatic cancer cells use to increase uptake of amino acids to meet the needs of rapid growth. Paradoxically, in non-Ras transformed medulloblastoma brain tumors, we have shown that expression and activation of the receptor tyrosine kinase TrkA overactivates macropinocytosis, resulting in the catastrophic disintegration of the cell membrane and in tumor cell death. The molecular basis of this uncontrolled form of macropinocytosis has not been previously understood. Here, we demonstrate that the overactivation of macropinocytosis is caused by the simultaneous activation of two TrkA-mediated pathways: (i) inhibition of RhoB via phosphorylation at Ser(185) by casein kinase 1, which relieves actin stress fibers, and (ii) FRS2-scaffolded Src and H-Ras activation of RhoA, which stimulate actin reorganization and the formation of lamellipodia. Since catastrophic macropinocytosis results in brain tumor cell death, improved understanding of the mechanisms involved will facilitate future efforts to reprogram tumors, even those resistant to apoptosis, to die.

Indexed as

PinocytosisActinsCasein Kinase ICell DeathCell Line, TumorCerebellar NeoplasmsHumansMedulloblastomaPhosphorylationProto-Oncogene Proteins p21(ras)Receptor, trkArhoA GTP-Binding ProteinrhoB GTP-Binding ProteinSerineSignal TransductionActinsCasein Kinase INTRK1 protein, humanProto-Oncogene Proteins p21(ras)Receptor, trkArhoA GTP-Binding ProteinRHOA protein, humanrhoB GTP-Binding ProteinSerine

Identifiers

PMID27503856
PMCPMC5038151
OpenAlexW2517299874

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.