title: Cyr61 promotes growth of pancreatic carcinoma via nuclear exclusion of p27.
abstract: The molecular regulation of the growth of pancreatic carcinoma (PCC) is complicated and not defined yet. Here we show that the cysteine-rich protein 61 (Cyr61) levels were significantly higher in PCC than in the adjacent nontumor tissues from the same human patient. Overexpression of Cyr61 enhanced the proliferation of PCC cells, while inhibition of Cyr61 decreased the proliferation of PCC cells. Further analysis showed that Cyr61 seemed to activate phosphatidylinositol 3-kinase (PI3K) but not extracellular-related kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway in PCC cells, which subsequently induced nuclear exclusion of a major cell cycle inhibitor, p27, to increase cell proliferation. Taken together, these findings reveal the molecular basis underlying Cyr61-regulated PCC proliferation, suggest a potential role of Cyr61 in PCC growth, and highlight Cyr61 as a novel target for PCC therapy.
authors.affiliation: Department of Integrative Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, 200032, Shanghai, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Shi
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yin
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Luming
authors.initials: L
authors.lastname: Liu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Meng
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism*; D055515:Cysteine-Rich Protein 61 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: C501848:CCN1 protein, human; C436291:CDKN1B protein, human; D055515:Cysteine-Rich Protein 61; D012333:RNA, Messenger; D050760:Cyclin-Dependent Kinase Inhibitor p27
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