Calpain: a role in cell transformation and migration

Neil O Carragher1, Margaret C Frame

  • 1The Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, G61 1BD Glasgow, Scotland, UK. n.carragher@beatson.gla.ac.uk

Insights

Calpain activity is crucial for cell migration and cancer progression. Genetic and molecular studies confirm calpain

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Calpains are calcium-dependent proteases with essential cellular functions.
  • Recent structural and genetic studies have illuminated calpain activation and roles.

Purpose of the Study:

  • To investigate the physiological roles of calpains in cellular processes.
  • To explore the involvement of calpains in oncogenic transformation and cell migration.

Main Methods:

  • Determining three-dimensional crystal structures of calpains.
  • Generating calpain knockout animal models.
  • Employing molecular intervention strategies and genetic ablation.
  • Analyzing Src and epidermal growth factor receptor (EGFR) stimulated cell motility.

Main Results:

  • Calpain activity is essential for actin cytoskeleton remodeling and cell migration.
  • Calpain promotes cell-cycle progression and anchorage-independent growth in Src-transformed cells.
  • In vivo studies link calpain levels and activity to tumor development and invasion.

Conclusions:

  • Calpain plays a significant role in promoting cell transformation and migration.
  • Calpain's functions have critical implications in cancer pathobiology.
  • Targeting calpain may offer therapeutic strategies for cancer treatment.

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, invadopodia can...
Cell-matrix's Response to Mechanical Forces01:13

Cell-matrix's Response to Mechanical Forces

In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue. 
Anchoring junctions mechanically attach a cell to the...
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 cells.
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...