Evidence map›Paper›PMID 22710722›Full record

ArticleOncogene2013

Adhesion-mediated cytoskeletal remodeling is controlled by the direct scaffolding of Src from FAK complexes to lipid rafts by SSeCKS/AKAP12.

B Su, L Gao, F Meng, L-W Guo, J Rothschild, I H Gelman

Abstract read
In one paragraph

Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.1field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. The scaffolding protein AKAP12 regulates mRNA localization and translation.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Paradoxical roles of dual oxidases in cancer biology.Free radical biology & medicine · 2017
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Scaffolding during the cell cycle by A-kinase anchoring proteins.Pflugers Archiv : European journal of physiology · 2015
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 1 country.

B SuDepartment of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
L Gao
F Meng
L-W Guo
J Rothschild
I H Gelman
Roswell Park Comprehensive Cancer Center · USCancer Genetics (United States) · USNational Center for Toxicological Research · USUniversity at Buffalo, State University of New York · US

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MARK G FRATTINI · 1985 to 2026
$116.6M
PKC/PKA Regulation in Prostate Cancer by SSeCKS/Gravin/AKAP12R01CA094108 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI GELMAN, IRWIN H. · 2002 to 2014
$2.8M
Loss of FLJ13639 Expression in Acute LeukemiaR01CA116430 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI SINGH, KESHAV K · 2006 to 2010
$1.4M
PKC/PKA in Prostate CancerR55CA094108 · NCI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI GELMAN, IRWIN H. · 2002 to 2002
$100k
NCI NIH HHS CA116430NCI NIH HHS CA94108NCI NIH HHS P30 CA016056NCI NIH HHS P30-CA016056NCI NIH HHS PC074228NCI NIH HHS PC101210NCI NIH HHS R01 CA094108NCI NIH HHS R01 CA116430NCI NIH HHS R55 CA094108
6 · The paper itself

Abstract

Metastatic cell migration and invasion are regulated by altered adhesion-mediated signaling to the actin-based cytoskeleton via activated Src-FAK complexes. Src-suppressed C-kinase substrate (SSeCKS, the rodent orthologue of human Gravin/AKAP12), whose expression is downregulated by oncogenic Src and in many human cancers, antagonizes oncogenic Src pathways including those driving neovascularization at metastatic sites, metastatic cell motility and invasiveness. This is likely manifested through its function as a scaffolder of F-actin and signaling proteins such as cyclins, calmodulin, protein kinase C and A. Here we show that in contrast to its ability to inhibit haptotaxis, SSeCKS increased prostate cancer cell adhesion to fibronectin and type I collagen in a FAK-dependent manner, correlating with a relative increase in FAK(poY397) levels. In contrast, SSeCKS suppressed adhesion-induced Src activation (Src(poY416)) and phosphorylation of FAK at Y925, a known Src substrate site. SSeCKS also induced increased cell spreading, cell flattening, integrin β1 clustering and formation of mature focal adhesion plaques. An in silico analysis identified a Src-binding domain on SSeCKS(aa 153-166) that is homologous to the Src-binding domain of caveolin-1, and this region is required for SSeCKS-Src interaction, for SSeCKS-enhanced Src activity and sequestration to lipid rafts and for SSeCKS-enhanced adhesion of MAT-LyLu and CWR22Rv1 prostate cancer cells. Our data suggest a model in which SSeCKS suppresses oncogenic motility by sequestering Src to caveolin-rich lipid rafts, thereby disengaging Src from FAK-associated adhesion and signaling complexes.

Indexed as

Actin CytoskeletonA Kinase Anchor ProteinsAmino Acid SequenceCaveolin 1Cell AdhesionCell Cycle ProteinsCell MovementChemotaxisCytoskeletonFocal Adhesion Kinase 1HumansIntegrin beta1Membrane MicrodomainsMolecular Sequence DataSignal Transductionsrc-Family KinasesAKAP12 protein, humanA Kinase Anchor ProteinsCaveolin 1Cell Cycle ProteinsFocal Adhesion Kinase 1Integrin beta1src-Family Kinases

Identifiers

PMID22710722
PMCPMC3449054
OpenAlexW1979445595

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.