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Interplay between oncogenic K-Ras and wild-type H-Ras in Caco2 cell transformation
Georgia Ikonomou1, Vassiliki Kostourou, Senji Shirasawa
1Institute of Molecular Oncology, Biomedical Sciences Research Center Alexander Fleming, Vari, Greece.
Journal of Proteomics
|July 18, 2012
Summary
Activating RAS gene mutations drive cancer progression. This study reveals how mutant KRAS and HRAS alter colorectal cancer cell proteomes, uncovering a novel K-ras and H-ras interaction impacting colorectal carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Proteomics
Background:
- RAS gene mutations are common oncogenic alterations in cancer.
- Activating RAS mutations promote colorectal adenoma to cancer progression.
Purpose of the Study:
- To identify proteome changes in Caco2 colorectal cancer cells expressing mutant KRAS(V12) and HRAS(V12).
- To investigate the interplay between oncogenic K-ras and endogenous H-ras in colorectal cancer.
Main Methods:
- Utilized 2D-gel electrophoresis and LC-MS/MS to analyze protein expression.
- Employed RNA interference (RNAi) to silence endogenous H-ras.
Main Results:
- Identified nearly 200 differentially expressed proteins between Caco2, Caco2-KRAS(V12), and Caco2-HRAS(V12) cells.
- Observed elevated endogenous H-ras in KRAS(V12)-transformed cells; silencing H-ras reversed some proteomic changes.
- HRAS silencing reduced invasiveness of Caco2-KRAS(V12) cells, linked to cytoskeletal and cell adhesion protein alterations.
Conclusions:
- Mutant KRAS partially exerts effects via endogenous H-ras activation.
- A novel interplay between K-ras and H-ras influences colorectal carcinogenesis.
- Proteomic alterations, particularly in cytoskeletal and adhesion proteins, are linked to cancer cell invasiveness.
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