title: Parkin deficiency contributes to pancreatic tumorigenesis by inducing spindle multipolarity and misorientation.
abstract: Parkin, an E3 ubiquitin ligase well known for its role in the pathogenesis of juvenile Parkinson disease, has been considered as a candidate tumor suppressor in certain types of cancer. It remains unknown whether parkin is involved in the development of pancreatic cancer, the fourth leading cause of cancer-related deaths worldwide. Herein, we demonstrate the downregulation and copy number loss of the parkin gene in human pancreatic cancer specimens. The expression of parkin negatively correlates with clinicopathological parameters indicating the malignancy of pancreatic cancer. In addition, knockdown of parkin expression promotes the proliferation and tumorigenic properties of pancreatic cancer cells both in vitro and in mice. We further find that parkin deficiency increases the proportion of cells with spindle multipolarity and multinucleation. Parkin-depleted cells also show a significant increase in spindle misorientation. These findings indicate crucial involvement of parkin deficiency in the pathogenesis of pancreatic cancer.
authors.affiliation: Key Laboratory of Protein Science and Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Jihui
authors.initials: J
authors.lastname: Hao
authors.forename: Dengwen
authors.initials: D
authors.lastname: Li
authors.forename: Youguang
authors.initials: Y
authors.lastname: Luo
authors.forename: Xiuchao
authors.initials: X
authors.lastname: Wang
authors.forename: Yunfan
authors.initials: Y
authors.lastname: Yang
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Wenqing
authors.initials: W
authors.lastname: Shui
authors.forename: Quan
authors.initials: Q
authors.lastname: Chen
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D015536:Down-Regulation; D018628:Gene Dosage; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C470243:KIF11 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D016547:Kinesins
keywords: cell proliferation; pancreatic cancer; parkin; spindle misorientation; spindle multipolarity