SPARC overexpression inhibits cell proliferation in neuroblastoma and is partly mediated by tumor suppressor protein PTEN and AKT
Authors: Jasti S Rao
Praveen Bhoopathi
Meena Gujrati
Bharathi Gorantla
Jeffrey D Klopfenstein
Christopher S Gondi
G S Sailaja
Journal: PloS one (2012)
Discipline: Multidisciplinary
Keywords: SPARC; neuroblastoma cells; radio-therapy; AKT; PTEN
Affiliations: Department of Cancer Biology and Pharmacology, University of Illinois College of Medicine at Peoria, Peoria, Illinois, United States of America.

Abstract:  Secreted protein acidic and rich in cysteine (SPARC) is also known as BM-40 or Osteonectin, a multi-functional protein modulating cell-cell and cell-matrix interactions. In cancer, SPARC is not only linked with a highly aggressive phenotype, but it also acts as a tumor suppressor. In the present study, we sought to characterize the function of SPARC and its role in sensitizing neuroblastoma cells to radio-therapy. SPARC overexpression in neuroblastoma cells inhibited cell proliferation in vitro. Additionally, SPARC overexpression significantly suppressed the activity of AKT and this suppression was accompanied by an increase in the tumor suppressor protein PTEN both in vitro and in vivo. Restoration of neuroblastoma cell radio-sensitivity was achieved by overexpression of SPARC in neuroblastoma cells in vitro and in vivo. To confirm the role of the AKT in proliferation inhibited by SPARC overexpression, we transfected neuroblastoma cells with a plasmid vector carrying myr-AKT. Myr-AKT overexpression reversed SPARC-mediated PTEN and increased proliferation of neuroblastoma cells in vitro. PTEN overexpression in parallel with SPARC siRNA resulted in decreased AKT phosphorylation and proliferation in vitro. Taken together, these results establish SPARC as an effector of AKT-PTEN-mediated inhibition of proliferation in neuroblastoma in vitro and in vivo. 

Retracted: Yes

PubPeer comments:
 Figure 1E. As highlighted with red rectangles, the non-IR panels from both cell types, left and right, appear to be showing the same photos. Could the authors please check? ![file] , 
 Figure 7C. Two panels in the SPARC row appear to show an area of overlap. Shown with cyan rectangles. ![file] , 
 Supplemental Figure 1B. Two of the three GAPDH panels appear to look unexpectedly similar, as shown in pink. ![file] , 
 #1 In addition to which, the SK-N-AS IR pEV panel appears to be the same as the SK-N-AS and NB1691 Non-IR Mock panels (green boxes). ![file] , 
 2020 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0228246 After publication of this article [1] concerns were raised about the following figures: The GAPDH western blot panel for IMR-32 in Fig 1B appears similar to the GAPDH panel for IMR-32 in Fig 2B. These represent the same experimental conditions. In Fig 1E, all of the corresponding Non-IR panels appear similar for SK-N-AS and NB1691. In addition, the Non-IR Mock panels appear similar to the IR, SK-N-AS, pEV panel. The GAPDH panel for SK-N-AS in Fig 2B appears similar to the GAPDH panel for NB1691 in Fig 3A. The GAPDH panel for IMR-32 in Fig 4A appears similar to the GAPDH panel for NB1691 in Fig 6A. In the IMR-32 pc-Jun (ser 63) blot shown in Fig 5, when levels are adjusted the background in lane 3 appears different than that in other lanes. In Fig 7C, there appears to be a region of overlap between SPARC panels for Non-IR Mock (upper left quadrant) and Non-IR pEV (lower right quadrant). In S1B Fig., the GAPDH panels for SK-N-AS and NB1691 appear similar. The University of Illinois at Chicago investigated this work and found evidence of data falsification involving Fig 1E. In light of the above concerns that call into question the validity and reliability of the reported results and following the outcome of the institutionu2019s investigation, the PLOS ONE Editors retract this article. The authors either did not reply to the retraction notification or could not be reached. Reference 1.Bhoopathi P, Gorantla B, Sailaja GS, Gondi CS, Gujrati M, Klopfenstein JD, et al. (2012) SPARC Overexpression Inhibits Cell Proliferation in Neuroblastoma and Is Partly Mediated by Tumor Suppressor Protein PTEN and AKT. PLoS ONE 7(5): e36093. https: doi.org 10.1371 journal.pone.0036093 pmid:22567126 ,