Abstract
Colorectal cancer (CRC) growth and progression is frequently driven by RAS pathway activation through upstream growth factor receptor activation or through mutational activation of KRAS or BRAF. Here we describe an additional mechanism by which the RAS pathway may be modulated in CRC. PTPRS, a receptor-type protein tyrosine phosphatase, appears to regulate RAS pathway activation through ERK. PTPRS modulates ERK phosphorylation and subsequent translocation to the nucleus. Native mutations in PTPRS, present in ~10% of CRC, may reduce its phosphatase activity while increasing ERK activation and downstream transcriptional signaling.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Cell Line, Tumor
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Cell Nucleus / metabolism*
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Colorectal Neoplasms / metabolism*
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Colorectal Neoplasms / pathology*
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Enzyme Activation
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ErbB Receptors / metabolism
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Extracellular Signal-Regulated MAP Kinases / metabolism*
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Gene Expression Regulation, Neoplastic
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Humans
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Mitogen-Activated Protein Kinase Kinases / metabolism
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Mutation / genetics
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Phosphorylation
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Protein Transport
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Proto-Oncogene Proteins c-akt / metabolism
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RNA, Small Interfering / metabolism
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Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism*
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Signal Transduction*
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ras Proteins / metabolism*
Substances
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RNA, Small Interfering
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ErbB Receptors
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Proto-Oncogene Proteins c-akt
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Extracellular Signal-Regulated MAP Kinases
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Mitogen-Activated Protein Kinase Kinases
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PTPRS protein, human
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Receptor-Like Protein Tyrosine Phosphatases, Class 2
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ras Proteins