GRIM-19 inhibits v-Src-induced cell motility by interfering with cytoskeletal restructuring.

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.

journal_name

Oncogene

journal_title

Oncogene

authors

Sun P,Nallar SC,Kalakonda S,Lindner DJ,Martin SS,Kalvakolanu DV

doi

10.1038/onc.2008.480

subject

Has Abstract

pub_date

2009-03-12 00:00:00

pages

1339-47

issue

10

eissn

0950-9232

issn

1476-5594

pii

onc2008480

journal_volume

28

pub_type

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