Abstract
Non-small-cell lung cancer (NSCLC) is a deadly disease due to lack of effective diagnosis biomarker and therapeutic target. Much effort has been made in defining gene defects in NSCLC, but its full molecular pathogenesis remains unexplored. Here, we found RACK1 (receptor of activated kinase 1) was elevated in most NSCLC, and its expression level correlated with key pathological characteristics including tumor differentiation, stage, and metastasis. In addition, RACK1 activated sonic hedgehog signaling pathway by interacting with and activating Smoothened to mediate Gli1-dependent transcription in NSCLC cells. And silencing RACK1 dramatically inhibited in vivo tumor growth and metastasis by blocking the sonic hedgehog signaling pathway. These results suggest that RACK1 represents a new promising diagnosis biomarker and therapeutic target for NSCLC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Biomarkers, Tumor / metabolism*
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Carcinoma, Non-Small-Cell Lung / diagnosis
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Carcinoma, Non-Small-Cell Lung / metabolism*
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Carcinoma, Non-Small-Cell Lung / pathology
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Carcinoma, Non-Small-Cell Lung / therapy
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GTP-Binding Proteins / metabolism*
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Hedgehog Proteins / metabolism*
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Humans
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Lung Neoplasms / diagnosis
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Lung Neoplasms / metabolism*
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Lung Neoplasms / pathology
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Lung Neoplasms / therapy
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Male
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Mice
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Mice, Nude
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Neoplasm Metastasis
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Neoplasm Proteins / metabolism*
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Neoplasm Transplantation
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Receptors for Activated C Kinase
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Receptors, Cell Surface / metabolism*
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Receptors, G-Protein-Coupled / metabolism
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Signal Transduction*
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Smoothened Receptor
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Transcription Factors / metabolism
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Transcription, Genetic
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Transplantation, Heterologous
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Zinc Finger Protein GLI1
Substances
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Biomarkers, Tumor
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GLI1 protein, human
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Hedgehog Proteins
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Neoplasm Proteins
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RACK1 protein, human
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Receptors for Activated C Kinase
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Receptors, Cell Surface
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Receptors, G-Protein-Coupled
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SHH protein, human
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SMO protein, human
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Smoothened Receptor
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Transcription Factors
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Zinc Finger Protein GLI1
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GTP-Binding Proteins