Evidence map›Paper›PMID 30282066›Full record

ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2018

Inhibition of Protein Phosphatase 2A Sensitizes Mucoepidermoid Carcinoma to Chemotherapy via the PI3K-AKT Pathway in Response to Insulin Stimulus.

Limin Liu, Herui Wang, Jing Cui, Qi Zhang, Wei Zhang, Wanlin Xu, Hao Lu, Shengwen Liu, Shukun Shen, Francia Fang and 4 more

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

Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

13 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Targeting PP2A for cancer therapeutic modulation.Cancer biology & medicine · 2022
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. 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

14 authors at 5 institutions in 2 countries.

Limin LiuDepartment of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, National Clinical Research Center for Oral Diseases, Shanghai, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Herui WangNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Jing CuiNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Qi ZhangNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Wei ZhangNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Wanlin XuDepartment of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, National Clinical Research Center for Oral Diseases, Shanghai, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Hao LuDepartment of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, National Clinical Research Center for Oral Diseases, Shanghai, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Shengwen LiuDepartment of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, National Clinical Research Center for Oral Diseases, Shanghai, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Shukun ShenDepartment of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, National Clinical Research Center for Oral Diseases, Shanghai, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Francia FangDuke University, Durham, North Carolina, USA.
Lei LiDepartment of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, National Clinical Research Center for Oral Diseases, Shanghai, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Wenjun YangDepartment of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, National Clinical Research Center for Oral Diseases, Shanghai, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Zhengping ZhuangNeuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
Jiang LiDepartment of Oral Pathology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, National Clinical Research Center for Oral Diseases, Shanghai, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.
Shanghai Jiao Tong University · CNShanghai Ninth People's Hospital · CNNational Institutes of Health · USNational Cancer Institute · USDuke University · US

Funding

Hypoxia signaling in cancer developmentZIABC011773 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ZHUANG, ZHENGPING · 2017 to 2025
$13.0M
Intramural NIH HHS ZIA BC011773
6 · The paper itself

Abstract

BACKGROUND/

aimsProtein phosphatase 2A (PP2A) is a ubiquitous serine/threonine phosphatase that mediates cell cycle regulation and metabolism. Mounting evidence has indicated that PP2A inhibition exhibits considerable anticancer potency in multiple types of human cancers. However, the efficacy of PP2A inhibition remains unexplored in mucoepidermoid carcinoma (MEC), especially in locally advanced and metastatic cases with limited systemic treatment. In this study, we demonstrated the therapeutic potency of LB100 in mucoepidermoid carcinoma.

methodsIn this study, the expression of PP2A was evaluated using immunohistochemical (IHC) staining. The effects associated with LB100 alone and in combination with cisplatin for the treatment of mucoepidermoid carcinoma were investigated both in vitro, regarding metabolism, proliferation, and migration, and in vivo in a mucoepidermoid carcinoma xenograft model. In addition, with LB100 treatment and in response to an insulin stimulus, the expression levels and phosphorylation levels of targets in the PI3K-AKT pathway were determined using western blot analysis and immunoblotting.

resultsThe expression of protein phosphatase 2A was significantly upregulated in the clinical specimens of high-grade MECs compared with those of low-/medium-grade MECs and normal controls. In this article, we report that a small molecule PP2A inhibitor, LB100, decreased cellular viability and glycolytic activity and induced G2/M cell cycle arrest. Importantly, LB100 enhanced the efficacy of cisplatin in mucoepidermoid carcinoma cells both in vitro and in vivo. PP2A inhibition by LB100 increased the phosphorylation of insulin receptor substrate 1(IRS-1) on serine residues, downregulated the expression of phosphatidylinositol 3-kinase (PI3K) p110 alpha subunit and dephosphorylated AKT at Ser473 and Thr308 in mucoepidermoid carcinoma cells in response to insulin stimulus.

conclusionThese results highlight the translational potential of PP2A inhibition to synergize with cisplatin in mucoepidermoid carcinoma treatment.

Indexed as

AdultAnimalsAntineoplastic AgentsBridged Bicyclo Compounds, HeterocyclicCarcinoma, MucoepidermoidCell Cycle CheckpointsCell Line, TumorCisplatinFemaleHumansInsulinInsulin Receptor Substrate ProteinsMaleMiceMice, NudeMiddle AgedAntineoplastic AgentsBridged Bicyclo Compounds, HeterocyclicCisplatinInsulinInsulin Receptor Substrate ProteinsLB100Phosphatidylinositol 3-KinasesPiperazinesProtein Phosphatase 2Proto-Oncogene Proteins c-aktChemotherapyLB100Mucoepidermoid carcinomaPI3K/AKT pathwayProtein phosphatase 2A

Identifiers

PMID30282066
PMCPMC8114738
OpenAlexW2895074875

What OpenQuestion holds

Textmetadata
LicenceTDM
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.