title: Suppression of Ubiquitin-Specific Peptidase 17 (USP17) Inhibits Tumorigenesis and Invasion in Non-Small Cell Lung Cancer Cells.
abstract: Recently, deubiquitinating enzymes (DUBs) are emerging as new regulators in cancer progression. However, understanding of the involvement of DUBs in non-small cell lung cancer (NSCLC) is just beginning. In this study, we investigated the expression and biological function of ubiquitin-specific peptidase 17 (USP17) in NSCLC progression in vitro and in vivo. We found that the expression of USP17 was higher than in a normal control. We further efficiently depleted USP17 expression in two different NSCLC cells, A549 and H1299. The anchorage-independent growth ability of these cells, estimated by soft agar colony formation assay, was significantly reduced after USP17 knockdown. Moreover, Matrigel-Transwell analysis showed that suppression of USP17 decreased cell migration and invasion capacity. Molecular mechanism studies found that USP17 silencing downregulated the expression of matrix metalloproteases (MMP3 and MMP9) in NSCLC cells. Furthermore, animal model results showed that USP17 suppression inhibited NSCLC tumorigenesis and growth. Altogether, this study illustrates the important functions of USP17 in NSCLC and suggests that USP17 might be an attractive target for NSCLC therapy.
authors.affiliation: Department of Chest Surgery, Qingpu Branch Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Shengchao
authors.initials: S
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.forename: Ruheng
authors.initials: R
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D047368:Tumor Burden
chemical_list: D034741:RNA, Small Interfering; D010450:Endopeptidases; C484854:USP17L2 protein, human; D020782:Matrix Metalloproteinases