Calreticulin Exposure in Mitotic Catastrophe

Lucillia Bezu1,2, Oliver Kepp1,2, Guido Kroemer3,4

  • 1Cell biology and metabomics platforms, Gustaver Roussy Cancer Campus, Villejuif, France.

Insights

Mitotic catastrophe, a cell death pathway, can be triggered by chemotherapy. This study presents a method to detect calreticulin exposure, a marker of immunogenic cell death, on tumor cells undergoing this process.

Area of Science:

  • Cell biology
  • Cancer research
  • Immunology

Background:

  • Mitotic catastrophe is a cell death pathway resulting from abnormal mitosis, often induced by DNA damage or cell cycle perturbations.
  • It can prevent cancer formation but also occur in cancer cells during therapy, with agents like vinca alkaloids and taxanes impacting microtubules.
  • Some agents inducing mitotic catastrophe also cause immunogenic cell death (ICD), characterized by cell-surface calreticulin exposure, which enhances anti-tumor immunity.

Purpose of the Study:

  • To describe a novel immunofluorescence-based cytofluorometric technique.
  • To detect calreticulin exposure on tumor cells.
  • To analyze drugs that induce mitotic catastrophe and immunogenic cell death.

Main Methods:

  • Development of an immunofluorescence-based cytofluorometric assay.
  • Application of the assay to detect cell-surface calreticulin exposure.
  • Utilizing tumor cells treated with drugs known to induce mitotic catastrophe.

Main Results:

  • Successful establishment of a technique to quantify calreticulin exposure.
  • Demonstration of calreticulin exposure on tumor cells treated with specific chemotherapeutic agents.
  • Validation of the method for assessing drug-induced immunogenic cell death.

Conclusions:

  • The described technique provides a reliable method for detecting calreticulin exposure, a key marker of immunogenic cell death.
  • This assay can be used to evaluate the immunogenic potential of drugs that induce mitotic catastrophe.
  • The findings contribute to understanding cancer cell death mechanisms and developing more effective immunotherapies.

Related Concept Videos

The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.4K
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
4.0K
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.4K
Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
4.6K
Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
5.5K
Nucleotide Excision Repair01:08

Nucleotide Excision Repair

Overview
39.5K