title: The SWI/SNF Complex Protein Snr1 Is a Tumor Suppressor inDrosophilaImaginal Tissues.
abstract: Components of the SWI/SNF chromatin-remodeling complex are among the most frequently mutated genes in various human cancers, yet only SMARCB1/hSNF5, a core member of the SWI/SNF complex, is mutated in malignant rhabdoid tumors (MRT). How SMARCB1/hSNF5 functions differently from other members of the SWI/SNF complex remains unclear. Here, we useDrosophilaimaginal epithelial tissues to demonstrate that Snr1, the conserved homolog of human SMARCB1/hSNF5, prevents tumorigenesis by maintaining normal endosomal trafficking-mediated signaling cascades. Removal of Snr1 resulted in neoplastic tumorigenic overgrowth in imaginal epithelial tissues, whereas depletion of any other members of the SWI/SNF complex did not induce similar phenotypes. Unlike other components of the SWI/SNF complex that were detected only in the nucleus, Snr1 was observed in both the nucleus and the cytoplasm. Aberrant regulation of multiple signaling pathways, including Notch, JNK, and JAK/STAT, was responsible for tumor progression uponsnr1-depletion. Our results suggest that the cytoplasmic Snr1 may play a tumor suppressive role inDrosophilaimaginal tissues, offering a foundation for understanding the pivotal role of SMARCB1/hSNF5 in suppressing MRT during early childhood.Cancer Res; 77(4); 862-73. ©2017 AACR.
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, Florida.
authors.forename: Gengqiang
authors.initials: G
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, the Chinese Academy of Sciences, Beijing, China.
authors.forename: Hanqing
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, Florida.
authors.forename: Dongyu
authors.initials: D
authors.lastname: Jia
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, Florida.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Shu
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, Florida.
authors.forename: William Hunt
authors.initials: WH
authors.lastname: Palmer
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, Florida.
authors.forename: Yi-Chun
authors.initials: YC
authors.lastname: Huang
authors.affiliation: The Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland.
authors.forename: Xiankun
authors.initials: X
authors.lastname: Zeng
authors.affiliation: The Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland.
authors.forename: Steven X
authors.initials: SX
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, the Chinese Academy of Sciences, Beijing, China. wumin@bio.fsu.edu rjiao@sun5.ibp.ac.cn.|Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, China.
authors.forename: Renjie
authors.initials: R
authors.lastname: Jiao
authors.affiliation: Department of Biological Science, Florida State University, Tallahassee, Florida. wumin@bio.fsu.edu rjiao@sun5.ibp.ac.cn.
authors.forename: Wu-Min
authors.initials: WM
authors.lastname: Deng
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000032:analysis / Q000502:physiology*; D004331:Drosophila melanogaster; D011992:Endosomes / Q000378:metabolism; D060227:Imaginal Discs / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D051880:Receptors, Notch / Q000502:physiology; D000071796:SMARCB1 Protein / Q000502:physiology; D050791:STAT Transcription Factors / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D000071796:SMARCB1 Protein; D050791:STAT Transcription Factors; C096659:Snr1 protein, Drosophila; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins