title: RACK1 promotes non-small-cell lung cancer tumorigenicity through activating sonic hedgehog signaling pathway.
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.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Shi
authors.forename: Yue-Zhen
authors.initials: YZ
authors.lastname: Deng
authors.forename: Jiang-Sha
authors.initials: JS
authors.lastname: Zhao
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Ji
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.forename: Yu-Xiong
authors.initials: YX
authors.lastname: Feng
authors.forename: Guo
authors.initials: G
authors.lastname: Li
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Li
authors.forename: Di
authors.initials: D
authors.lastname: Zhu
authors.forename: H Phillip
authors.initials: HP
authors.lastname: Koeffler
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhao
authors.forename: Dong
authors.initials: D
authors.lastname: Xie
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D019204:GTP-Binding Proteins / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D000072086:Smoothened Receptor; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous; D000071676:Zinc Finger Protein GLI1
chemical_list: D014408:Biomarkers, Tumor; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491023:SMO protein, human; D000072086:Smoothened Receptor; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D019204:GTP-Binding Proteins