title: Sam68 regulates cell proliferation and cell adhesion-mediated drug resistance (CAM-DR) via the AKT pathway in non-Hodgkin's lymphoma.
abstract: OBJECTIVE
  Sam68 (Src-associated in mitosis 68 kDa), a substrate for tyrosine kinase c-Src during mitosis, is up-regulated in a variety of human cancers and acts oncogenically promoting tumour progression. This study has explored biological function and clinical significance of Sam68 in non-Hodgkin's lymphoma (NHL).
  
  
  METHODS
  To examine Sam68 expression in NHL, clinically, eight diffuse large B-cell lymphomas and four reactive lymphoid hyperplasia fresh-frozen tissues were obtained for western blot and quantitative real-time PCR analyses. Using immunohistochemical staining, paraffin wax embedded sections from 164 cases of NHL patients were used to evaluate prognostic value of Sam68. Cell Counting Kit-8 (CCK-8) and soft agar colony assays were conducted to investigate the role of Sam68 in cell viability and cell proliferation respectively. Furthermore, effects of Sam68 on cell adhesion-mediated drug resistance (CAM-DR) was determined by CCK-8 assay and flow cytometric analysis.
  
  
  RESULTS
  Expression status of Sam68 inversely correlated with clinical outcomes of patients with NHL, and it was also an independent prognostic factor for the outcomes. In addition, Sam68 was associated with proliferation of NHL cells. Knock-down of its gene inhibited cell proliferation and colony formation by delaying cell cycle progression. Furthermore, OCI-Ly8 and Jeko-1 cells adhering to FN and HS-5 expressed higher Sam68 protein, compared to their suspension counterparts. Sam68 promoted cell adhesion-mediated drug resistance (CAM-DR) via the AKT pathway.
  
  
  CONCLUSIONS
  Increased Sam68 expression in NHL resulted in poor prognosis, and it promoted CAM-DR in NHL via AKT.
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors.forename: Yaxun
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Oncology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Miao
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors.forename: Haibing
authors.initials: H
authors.lastname: Yin
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors.forename: Chunsun
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors.forename: Yushan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Lu
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu, China.
authors.forename: Yuchan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Affiliated Cancer Hospital of Nantong University, Nantong, 226361, Jiangsu, China.
authors.forename: Song
authors.initials: S
authors.lastname: He
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D018920:Coculture Techniques; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C489559:KHDRBS1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051057:Proto-Oncogene Proteins c-akt