Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
SUMO-modified insulin-like growth factor 1 receptor (IGF-1R) increases cell cycle progression and cell proliferation
Karolinska Inst, Dept Pathol & Oncol, CCK R8 04, Stockholm, Sweden..
Karolinska Inst, Dept Pathol & Oncol, CCK R8 04, Stockholm, Sweden.;Guangdong Ocean Univ, Fisheries Coll, Lab Aquat Anim Nutr Feed, Zhanjiang, Peoples R China..
Karolinska Inst, Dept Pathol & Oncol, CCK R8 04, Stockholm, Sweden..
Karolinska Inst, Dept Pathol & Oncol, CCK R8 04, Stockholm, Sweden..
Show others and affiliations
2017 (English)In: Journal of Cellular Physiology, ISSN 0021-9541, E-ISSN 1097-4652, Vol. 232, no 10, p. 2722-2730Article in journal (Refereed) Published
Abstract [en]

Increasing number of studies have shown nuclear localization of the insulin-like growth factor 1 receptor (nIGF-1R) in tumor cells and its links to adverse clinical outcome in various cancers. Any obvious cell physiological roles of nIGF-1R have, however, still not been disclosed. Previously, we reported that IGF-1R translocates to cell nucleus and modulates gene expression by binding to enhancers, provided that the receptor is SUMOylated. In this study, we constructed stable transfectants of wild type IGF1R (WT) and triple-SUMO-site-mutated IGF1R (TSM) using igf1r knockout mouse fibroblasts (R-). Cell clones (R-WT and R-TSM) expressing equal amounts of IGF1R were selected for experiments. Phosphorylation of IGF-1R, Akt, and Erk upon IGF-1 stimulation was equal in R-WT and R-TSM. WT was confirmed to enter nuclei. TSM did also undergo nuclear translocation, although to a lesser extent. This may be explained by that TSM heterodimerizes with insulin receptor, which is known to translocate to cell nuclei. R-WT proliferated substantially faster than R-TSM, which did not differ significantly from the empty vector control. Upon IGF-1 stimulationG1-S-phase progression of R-WT increased from 12 to 38%, compared to 13 to 20% of R-TSM. The G1-S progression of R-WT correlated with increased expression of cyclin D1, A, and CDK2, as well as downregulation of p27. This suggests that SUMO-IGF-1R affects upstream mechanisms that control and coordinate expression of cell cycle regulators. Further studies to identify such SUMO-IGF-1R dependent mechanisms seem important.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017. Vol. 232, no 10, p. 2722-2730
Keyword [en]
cancer, cell cycle, IGF-1R, proliferation, SUMOylation
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-334029DOI: 10.1002/jcp.25818ISI: 000407019900014PubMedID: 28112398OAI: oai:DiVA.org:uu-334029DiVA, id: diva2:1159454
Available from: 2017-11-22 Created: 2017-11-22 Last updated: 2017-11-22Bibliographically approved

Open Access in DiVA

fulltext(1279 kB)14 downloads
File information
File name FULLTEXT01.pdfFile size 1279 kBChecksum SHA-512
2af51139e7e5bbd98c14310da8be47758f70d5e9333614ee8fd3ffbeb51449bae40d294411ef317d194742ccef601eeeba6efcce5bdb60414b859b85bd6c079d
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Agarwal, PrasoonJernberg Wiklund, Helena
By organisation
Experimental and Clinical Oncology
In the same journal
Journal of Cellular Physiology
Cell Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 14 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 303 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf