Evidence map›Paper›PMID 30553276›Full record

ArticleMolecular cancer2018

C-Src confers resistance to mitotic stress through inhibition DMAP1/Bub3 complex formation in pancreatic cancer.

Jingjie Li, Bin Hu, Ting Wang, Wenhua Huang, Chunmin Ma, Qin Zhao, Lingang Zhuo, Tao Zhang, Yuhui Jiang

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

Article in Molecular cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.5field-weighted citation impact, top 36% 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

11 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Research progress of Bub3 gene in malignant tumors.Cell biology international · 2022
    Review
  10. Article
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 1 country.

Jingjie LiThe Institute of Cell Metabolism, Shanghai Key Laboratory of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200080, China.
Bin HuThe Institute of Cell Metabolism, Shanghai Key Laboratory of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200080, China.
Ting WangDepartment of Pharmacology, College of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Wenhua HuangThe Institute of Cell Metabolism, Shanghai Key Laboratory of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200080, China.
Chunmin MaThe Institute of Cell Metabolism, Shanghai Key Laboratory of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200080, China.
Qin ZhaoThe Institute of Cell Metabolism, Shanghai Key Laboratory of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200080, China.
Lingang ZhuoThe Institute of Cell Metabolism, Shanghai Key Laboratory of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200080, China.
Tao ZhangDepartment of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200080, China.
Yuhui JiangThe Institute of Cell Metabolism, Shanghai Key Laboratory of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200080, China. yhjiang@shsmu.edu.cn.
Shanghai First People's Hospital · CNShanghai Jiao Tong University · CNTianjin Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundChromatin modification at mitosis is closely related to transcriptional reactivation in the subsequent cell cycle. We reasoned this process is deregulated by oncogenic signals, which would contribute to mitotic stress resistance in pancreatic cancer. Here, we show DMAP1/Bub3 complex mediates mitotic stress-induced cellular apoptosis, while this effect is counteracted by c-Src in pancreatic cancer cells. Our study aims to uncover an unidentified mechanism underlying the distinct response to mitotic stress between normal cells and pancreatic cancer cells.

methodsThe interaction between Bub3 and DMAP1 upon mitotic stress signaling was determined through molecular and cell biological methods. The inhibitory effect of c-Src on DMAP1/Bub3-mediated DNA methylation and gene transcription profile was investigated. The association between c-Src-mediated DMAP1 phosphorylation and paclitaxel activity in vivo and clinicopathologic characteristics were analyzed.

resultsMitotic arrest induced p38-dependent phosphorylation of Bub3 at Ser211, which promotes DMAP1/Bub3 interaction. DMAP1/Bub3 complex is recruited by TAp73 to the promoter of anti-apoptotic gene BCL2L1, thus mediates the DNA methylation and represses gene transcription linked to cell apoptosis. Meanwhile, DMAP1 was highly phosphorylated at Tyr 246 by c-Src in pancreatic cancer cells, which impedes DMAP1/Bub3 interaction and the relevant cellular activites. Blocking DMAP1 pTyr-246 potentiates paclitaxel-inhibited tumor growth. Clinically, DMAP1 Tyr 246 phosphorylation correlates with c-Src activity in human pancreatic cancer specimens and poor prognosis in pancreatic cancer patients.

conclusionsOur findings reveal a regulatory role of Bub3 in DMAP1-mediated DNA methylation upon mitotic stress and provide the relevance of DMAP1 pTyr-246 to mitotic stress resistance during pancreatic cancer treatment.

Indexed as

AnimalsApoptosisCell Cycle ProteinsCell Line, TumorCSK Tyrosine-Protein KinaseDNA MethylationHeterograftsHumansMaleMiceMice, NudeMitosisPancreatic NeoplasmsPhosphorylationPoly-ADP-Ribose Binding ProteinsRepressor ProteinsBUB3 protein, humanCell Cycle ProteinsCSK protein, humanCSK Tyrosine-Protein KinaseDMAP1 protein, humanPoly-ADP-Ribose Binding ProteinsRepressor Proteinssrc-Family KinasesMitosis,transcriptional reactivation,tumourigenesis,Bub3,p38,DMAP1,c-Src

Identifiers

PMID30553276
PMCPMC6295060
OpenAlexW2905539288

What OpenQuestion 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 OpenQuestion graph.