title: Silencing of CKIP-1 promotes tumor proliferation and cell adhesion-mediated drug resistance via regulating AKT activity in non-Hodgkin's lymphoma.
abstract: Casein kinase 2 interacting protein-1 (CKIP-1; also known as PLEKHO1) is involved in regulating many processes such as cell proliferation, differentiation and apoptosis. CKIP-1 also plays an important role in many types of cancer, such as colon, breast cancer and human osteosarcoma. In the present study, we found that CKIP-1 was reversely associated with the proliferation of non-Hodgkin's lymphoma (NHL) and cell adhesion mediated drug resistance (CAM-DR). We demonstrated that knockdown of CKIP-1 promoted the proliferation of NHL cells through interacting with Akt and suppressing Akt phosphorylation. In addition, adhesion of lymphoma cells to fibronectin or stroma cells (HS-5 cells) decreased CKIP-1 expression, which led to the upregulation of Akt phosphorylation. Importantly, we showed that the phosphorylation of Akt was correlated with CAM-DR phenotype in NHL cells. Taken together, the present study shed new light on the molecular mechanism of CAM-DR in NHL and targeting CKIP-1 may be a novel therapeutic target for NHL.
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu 226361, P.R. China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhong
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Qiru
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Ding
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu 22600, P.R. China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Hematology, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu 22600, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, Jiangsu 226361, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: He
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000473:pathology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C408877:PLEKHO1 protein, human; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt