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Published on: May 30, 2011
Targeted Quantitative Kinome Analysis Identifies PRPS2 as a Promoter for Colorectal Cancer Metastasis
1Department of Chemistry , University of California , Riverside , California 92521-0403 , United States.
Abstract:
Kinases are among the most important families of enzymes involved in cell signaling. In this study, we employed a recently developed parallel-reaction monitoring (PRM)-based targeted proteomic method to examine the reprogramming of the human kinome during colorectal cancer (CRC) metastasis. We were able to quantify the relative expression of 299 kinase proteins in a pair of matched primary/metastatic CRC cell lines. We also found that, among the differentially expressed kinases, phosphoribosyl pyrophosphate synthetase 2 (PRPS2) promotes the migration and invasion of cultured CRC cells through regulating the activity of matrix metalloproteinase 9 (MMP-9) and the expression of E-cadherin. Moreover, we found that the up-regulation of PRPS2 in metastatic CRC cells could be induced by the MYC proto-oncogene. Together, our unbiased kinome profiling approach led to the identification, for the first time, of PRPS2 as a promoter for CRC metastasis.
Insights
Researchers identified phosphoribosyl pyrophosphate synthetase 2 (PRPS2) as a key driver of colorectal cancer (CRC) metastasis. This kinase promotes cell migration and invasion, offering new therapeutic targets for CRC.
Area of Science:
- Molecular Biology
- Oncology
- Proteomics
Background:
- Kinases are crucial enzymes in cellular signaling pathways.
- Colorectal cancer (CRC) metastasis involves complex molecular reprogramming.
- Understanding kinome alterations is vital for cancer research.
Purpose of the Study:
- To investigate kinome reprogramming during colorectal cancer (CRC) metastasis.
- To identify novel kinase regulators of CRC cell migration and invasion.
- To elucidate the role of specific kinases in metastatic progression.
Main Methods:
- Utilized parallel-reaction monitoring (PRM)-based targeted proteomics.
- Quantified relative expression of 299 kinase proteins in matched primary/metastatic CRC cell lines.
- Investigated the functional impact of identified kinases on CRC cell behavior.
Main Results:
- Identified differentially expressed kinases during CRC metastasis.
- Phosphoribosyl pyrophosphate synthetase 2 (PRPS2) was found to promote CRC cell migration and invasion.
- PRPS2 regulates matrix metalloproteinase 9 (MMP-9) activity and E-cadherin expression.
- MYC proto-oncogene was identified as an inducer of PRPS2 up-regulation in metastatic CRC cells.
Conclusions:
- PRPS2 is a novel promoter of colorectal cancer metastasis.
- Kinome profiling provides insights into metastatic mechanisms.
- Targeting PRPS2 may offer a therapeutic strategy for advanced CRC.
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