GRIM-19 inhibits v-Src-induced cell motility by interfering with cytoskeletal restructuring
Authors: S Kalakonda
P Sun
S C Nallar
S S Martin
D V Kalvakolanu
D J Lindner
Journal: Oncogene (2009)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: GRIM-19; tumor suppressor; v-Src; cell motility; cytoskeletal remodeling
Affiliations: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.

Abstract:  GRIM-19 (Gene associated with Retinoid-Interferon-induced Mortality 19) is a novel tumor suppressor regulated by interferon/retinoid combination. We have recently shown that GRIM-19 inhibits v-Src-induced oncogenic transformation and metastatic behavior of cells. Oncogenic v-Src induces cell motility by cytoskeletal remodeling, especially the formation of podosomes and. Here, we show that GRIM-19 inhibited the v-Src-induced cell motility by inhibiting cytoskeletal remodeling, that is, podosome formation. We also show that the N terminus of GRIM-19 played a major role in this process and identified critical residues in this region. More importantly, we show that tumor-associated GRIM-19 mutations disrupted its ability to inhibit v-Src-induced cell motility. These actions appear to occur independently of STAT3, a known target of GRIM-19-mediated inhibition. Lastly, tumor-associated GRIM-19 mutants significantly lost their ability to control v-Src-induced metastases in vivo, indicating the biological and pathological significance of these observations. 

Retracted: No

PubPeer comments:
  A standard retinotopic procedure was employed to define borders of visually responsive cortical areas (V1, V2, V3, V4v, and VO1). To my knowledge, there is no  standard procedure for the above purpose, nor is any method so standardized as not to require choices on the part of the investigator - as the below-quoted excerpts from the literature attest. It would be useful if the authors provided some more detail on their particular procedure, as this would seem essential to any replication attempts.  The most common approach is to encode the response phase for a slowly moving visual stimulus and to present the result on an individual s reconstructed cortical surface. The main aims of this study were to develop complementary general linear model (GLM)-based retinotopic mapping methods and to characterize the inter-individual variability of the visual area positions on the cortical surface. Henriksson et al (2012).  FMRI retinotopic mapping is a non-invasive technique for the delineation of low-level visual areas in individual subjects. It generally relies upon the analysis of functional responses to periodic visual stimuli that encode eccentricity or polar angle in the visual field. This technique is used in vision research when the precise assignation of brain activation to retinotopic areas is an issue. It involves processing steps computed with different algorithms and embedded in various software suites. Manual intervention may be needed for some steps. **Although the diversity of the available processing suites and manual interventions may potentially introduce some differences in the final delineation of visual areas, no documented comparison between maps obtained with different procedures has been reported in the literature.** To explore the effect of the processing steps on the quality of the maps obtained, we used two tools, BALC, which relies on a fully automated procedure, and BrainVoyager, where areas are delineated u201cby handu201d on the brain surface. Bordier et al (2015)  We present in this report a new method for retinotopic mapping of the human visual cortext using fMRI...Lastly, we present the choices we made to delineate these areas and extract regions of interest... (Wotawa et al (2006). ,