Evidence mapPaperPMID 34831139Full record

ArticleCells2021

Suppression of PI3K/Akt/mTOR/c-Myc/mtp53 Positive Feedback Loop Induces Cell Cycle Arrest by Dual PI3K/mTOR Inhibitor PQR309 in Endometrial Cancer Cell Lines.

I-Lun Hsin, Huang-Pin Shen, Hui-Yi Chang, Jiunn-Liang Ko, Po-Hui Wang

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. 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 6% 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, 47 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Silencing PPP2R1A inhibits the progression of gastric cancer cells.Journal of cancer research and clinical oncology · 2025
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Development, synthesis and validation of improved c-Myc/Max inhibitors.Journal of cellular and molecular medicine · 2024
    Article
  17. Article
  18. Article
  19. Article
  20. Review
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

5 authors at 2 institutions in 1 country.

I-Lun HsinInstitute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.ORCID 0000-0003-4711-3582
Huang-Pin ShenInstitute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
Hui-Yi ChangInstitute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
Jiunn-Liang KoInstitute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.ORCID 0000-0001-6855-9239
Po-Hui WangInstitute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
Chung Shan Medical University Hospital · TWChung Shan Medical University · TW

Funding

Taiwan Ministry of Science and Technology MOST 107-2314-B-040-017-MY3
6 · The paper itself

Abstract

Gene mutations in PIK3CA, PIK3R1, KRAS, PTEN, and PPP2R1A commonly detected in type I endometrial cancer lead to PI3K/Akt/mTOR pathway activation. Bimiralisib (PQR309), an orally bioavailable selective dual inhibitor of PI3K and mTOR, has been studied in preclinical models and clinical trials. The aim of this study is to evaluate the anticancer effect of PQR309 on endometrial cancer cells. PQR309 decreased cell viability in two-dimensional and three-dimensional cell culture models. PQR309 induced G1 cell cycle arrest and little cell death in endometrial cancer cell lines. It decreased CDK6 expression and increased p27 expression. Using the Proteome Profiler Human XL Oncology Array and Western blot assay, the dual inhibitor could inhibit the expressions of c-Myc and mtp53. KJ-Pyr-9, a c-Myc inhibitor, was used to prove the role of c-Myc in endometrial cancer survival and regulating the expression of mtp53. Knockdown of mtp53 lowered cell proliferation, Akt/mTOR pathway activity, and the expressions of c-Myc. mtp53 silence enhanced PQR309-inhibited cell viability, spheroid formation, and the expressions of p-Akt, c-Myc, and CDK6. This is the first study to reveal the novel finding of the PI3K/mTOR dual inhibitor in lowering cell viability by abolishing the PI3K/Akt/mTOR/c-Myc/mtp53 positive feedback loop in endometrial cancer cell lines.

Indexed as

Feedback, PhysiologicalAutophagyCell Cycle CheckpointsCell DeathCell Line, TumorCell ProliferationCell SurvivalEndometrial NeoplasmsFemaleHumansModels, BiologicalMutant ProteinsNeoplastic Stem CellsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktMutant ProteinsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mycTOR Serine-Threonine KinasesTumor Suppressor Protein p53c-Mycdual PI3K/mTOR inhibitorendometrial cancermutant p53PQR309

Identifiers

PMID34831139
PMCPMC8616154
OpenAlexW3210489126

What Socratic 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 Socratic graph.