Related Experiment Video

Updated: Feb 1, 2026

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

14.0K

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

Jingjie Li1, Bin Hu1,2, Ting Wang3

  • 1The Institute of Cell Metabolism, Shanghai Key Laboratory of Pancreatic Disease, Shanghai General Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, 200080, China.

Molecular Cancer
|December 17, 2018
PubMed
Abstract

Insights

DMAP1/Bub3 complex normally triggers apoptosis after mitotic stress, but c-Src in pancreatic cancer blocks this. Targeting DMAP1 phosphorylation enhances cancer treatment efficacy.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Epigenetics

Background:

  • Chromatin modification during mitosis is crucial for cell cycle progression and is often dysregulated in cancer.
  • Oncogenic signals can promote resistance to mitotic stress, a hallmark of pancreatic cancer.
  • The distinct responses to mitotic stress between normal and cancerous cells remain incompletely understood.

Purpose of the Study:

  • To elucidate the mechanism by which pancreatic cancer cells resist mitotic stress.
  • To investigate the role of the DMAP1/Bub3 complex in mediating apoptosis upon mitotic stress.
  • To determine how c-Src signaling counteracts DMAP1/Bub3-mediated apoptosis in pancreatic cancer.

Main Methods:

  • Utilized molecular and cell biology techniques to study DMAP1/Bub3 interactions under mitotic stress.
  • Investigated the impact of c-Src on DMAP1/Bub3-mediated DNA methylation and gene transcription.
  • Analyzed the correlation between c-Src-mediated DMAP1 phosphorylation, in vivo paclitaxel activity, and clinicopathologic features.

Main Results:

  • Mitotic arrest induces p38-dependent Bub3 phosphorylation, promoting DMAP1/Bub3 complex formation and recruitment to the BCL2L1 promoter, leading to DNA methylation and repression of apoptosis.
  • In pancreatic cancer cells, c-Src phosphorylates DMAP1 at Tyr 246, disrupting DMAP1/Bub3 interaction and inhibiting apoptosis.
  • Inhibition of DMAP1 Tyr 246 phosphorylation enhances paclitaxel's anti-tumor effects, and this phosphorylation correlates with c-Src activity and poor prognosis in patients.

Conclusions:

  • Bub3 plays a regulatory role in DMAP1-mediated DNA methylation in response to mitotic stress.
  • DMAP1 phosphorylation at Tyr 246 is a key factor in mitotic stress resistance in pancreatic cancer.
  • Targeting DMAP1 pTyr-246 represents a potential therapeutic strategy to overcome treatment resistance in pancreatic cancer.
Keywords:
Mitosis,transcriptional reactivation,tumourigenesis,Bub3,p38,DMAP1,c-Src

More Related Videos

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies07:29

Studying Pancreatic Cancer Stem Cell Characteristics for Developing New Treatment Strategies

Published on: June 20, 2015

20.2K
Isolation of Stem Cells from Human Pancreatic Cancer Xenografts11:44

Isolation of Stem Cells from Human Pancreatic Cancer Xenografts

Published on: September 26, 2010

22.8K

Related Concept Videos

Formation of Complex Ions03:45

Formation of Complex Ions

A type of Lewis acid-base chemistry involves the formation of a complex ion (or a coordination complex) comprising a central atom, typically a transition metal cation, surrounded by ions or molecules called ligands. These ligands can be neutral molecules like H2O or NH3, or ions such as CN− or OH−. Often, the ligands act as Lewis bases, donating a pair of electrons to the central atom. These types of Lewis acid-base reactions are examples of a broad subdiscipline called coordination...
26.1K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.8K
Responses to Salt Stress02:02

Responses to Salt Stress

Salt stress—which can be triggered by high salt concentrations in a plant’s environment—can significantly affect plant growth and crop production by influencing photosynthesis and the absorption of water and nutrients.
14.6K
The Mitotic Spindle02:27

The Mitotic Spindle

The mitotic spindle—or spindle apparatus—is a eukaryotic, cytoskeletal structure made up of long protein fibers called microtubules. Formed during cell division, the spindle separates sister chromatids and moves them to opposite ends of a parental cell, where the now individual chromosomes are distributed to two daughter cell nuclei.
The bipolar configuration of the mitotic spindle facilitates chromosomal segregation, preparing the cell for division. One mechanism that ensures...
8.0K
Feedback Inhibition00:46

Feedback Inhibition

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
57.1K
Responses to Heat and Cold Stress02:45

Responses to Heat and Cold Stress

Every organism has an optimum temperature range within which healthy growth and physiological functioning can occur. At the ends of this range, there will be a minimum and maximum temperature that interrupt biological processes.
14.8K