Related Experiment Video

Updated: May 3, 2026

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry
05:29

Measuring Caspase Activity Using a Fluorometric Assay or Flow Cytometry

Published on: March 24, 2023

7.7K

Caspase-8 as a regulator of tumor cell motility

R P Graf, N Keller, S Barbero

  • 1University of California San Diego, Moores Cancer Center, Department of Reproductive Medicine, 0803, 3855 Health Sciences Dr., La Jolla, CA 92093, USA. dstupack@ucsd.edu.

Current Molecular Medicine
|January 29, 2014
PubMed

Insights

Caspase-8, beyond cell death, drives cell migration and differentiation. Its peripheral localization influences cell fate and metastasis, indicating a context-dependent role in cancer progression.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Oncology

Background:

  • Caspases are cysteine proteases primarily known for regulating programmed cell death (apoptosis).
  • Caspase-8 has diverse functions beyond apoptosis, including immune signaling, differentiation, and cell migration.
  • Loss of caspase-8 expression results in embryonic lethality, highlighting its critical developmental roles.

Purpose of the Study:

  • To elucidate the non-apoptotic functions of caspase-8, particularly its role in cell migration and cancer.
  • To investigate the molecular mechanisms and cellular localization of caspase-8 during migration and metastasis.
  • To assess the clinical implications of caspase-8 expression in cancer prognosis.

Main Methods:

  • Investigated caspase-8 localization in the cellular periphery, specifically at focal adhesions and early endosomes.
  • Utilized in vitro cell migration assays and in vivo metastasis models.
  • Examined tyrosine-kinase dependent interactions of caspase-8 with focal adhesion components.

Main Results:

  • Caspase-8 localization at the cell periphery is crucial for both apoptosis and cell migration.
  • Caspase-8 interacts with focal adhesion complexes and early endosomes, enhancing focal adhesion turnover and integrin recycling.
  • These interactions promote cell migration in vitro and metastasis in vivo.
  • Tyrosine kinase activity is essential for caspase-8's pro-migratory function.

Conclusions:

  • Caspase-8 plays a significant role in cell migration and metastasis by modulating focal adhesion dynamics.
  • The pro-migratory function of caspase-8 is context-dependent and relies on its peripheral localization and interactions.
  • Caspase-8 expression may not always be a favorable prognostic indicator in cancer, suggesting a complex role in tumor progression.

More Related Videos

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

8.5K
Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

2.1K

Related Concept Videos

Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.5K
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
8.7K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.6K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.5K
Actin Polymerization and Cell Motility01:13

Actin Polymerization and Cell Motility

Actin is a family of globular proteins that are highly abundant in eukaryotic cells. It makes up approximately 1-5% of total cell protein concentration. Actin monomers polymerize to form a complex network of polarized filaments, the actin cytoskeleton, that plays a crucial role in many cellular processes, including cell motility, division, endocytosis, and metastasis of cancer cells.
Actin cytoskeleton dynamics can produce pushing, pulling, and resistance forces that help the cell to migrate....
5.8K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
5.7K