Related Experiment Videos
Calpain activity is generally elevated during transformation but has oncogene-specific biological functions
N O Carragher1, B D Fonseca, M C Frame
1The Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Glasgow G61 1BD, Scotland, UK. n.carragher@beatson.gla.ac.uk
Neoplasia (New York, N.Y.)
|April 8, 2004
Summary
Calpain activity is crucial for cancer cell transformation induced by various oncogenes, promoting key events like cell migration and growth. Inhibiting calpain may offer a general strategy against cancer by targeting activated proto-oncogenes.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Calpains, a family of cysteine proteases, are known to interact with oncogene and tumor-suppressor gene products.
- Calpain activity is implicated in cellular transformation and tumor invasion processes.
Purpose of the Study:
- To investigate the general association between calpain activity and cellular transformation.
- To elucidate the specific contributions of calpain to oncogene function during transformation.
Main Methods:
- Assessing calpain activity in cells transformed by various oncoproteins (v-Src, v-Jun, v-Myc, k-Ras, v-Fos).
- Evaluating the effects of calpain inhibition on cellular processes like focal adhesion remodeling, actin cytoskeleton dynamics, migration, and anchorage-independent growth.
- Analyzing the proteolysis of specific calpain substrates.
Main Results:
- Calpain activity was enhanced in cells transformed by v-Src, v-Jun, v-Myc, k-Ras, and v-Fos.
- Elevated calpain activity generally promoted focal adhesion remodeling, actin cytoskeleton disruption, morphological transformation, and cell migration.
- While v-Fos-transformed cells showed less dependence on calpain for certain events, anchorage-independent growth of all transformed cells was sensitive to calpain inhibition.
- Calpain activity was linked to oncogene-induced apoptosis in v-Myc-transformed cells.
Conclusions:
- Calpain activity is essential for the complete cellular transformation induced by common oncoproteins.
- Calpain plays distinct roles in oncogenic events driven by individual transforming proteins.
- Targeting calpain activity presents a potential therapeutic strategy for interfering with activated proto-oncogenes in cancer.