Evidence map›Paper›PMID 19802010›Full record

ArticleOncogene2010

RalA suppresses early stages of Ras-induced squamous cell carcinoma progression.

A G Sowalsky, A Alt-Holland, Y Shamis, J A Garlick, L A Feig

Open access · greenAbstract read
In one paragraph

Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

11 citing papers in PubMed, 23 citations in OpenAlex.

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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

5 authors at 1 institution in 1 country.

A G SowalskySackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA.
A Alt-Holland
Y Shamis
J A Garlick
L A Feig
Tufts University · US

Funding

FUNCTION OF THE RAS-RELATED RAL PROTEINSR01GM047717 · NIGMS · TUFTS UNIVERSITY BOSTON · PI FEIG, LARRY · 1992 to 2013
$4.8M
Genetic Analysis of Ras and G Protein FunctionR01MH083324 · NIMH · TUFTS UNIVERSITY BOSTON · PI FEIG, LARRY · 2009 to 2013
$2.6M
Function of the Ras Related Ral ProteinsR56GM047717 · NIGMS · TUFTS UNIVERSITY BOSTON · PI FEIG, LARRY · 2009 to 2009
$480k
NIGMS NIH HHS R01 GM047717NIGMS NIH HHS R56 GM047717NIMH NIH HHS R01 MH083324
6 · The paper itself

Abstract

Ras proteins activate Raf and PI-3 kinases, as well as exchange factors for RalA and RalB GTPases. Many previous studies have reported that the Ral-signaling cascade contributes positively to Ras-mediated oncogenesis. Here, using a bioengineered tissue model of early steps in Ras-induced human squamous cell carcinoma of the skin, we found the opposite. Conversion of Ras-expressing keratinocytes from a premalignant to malignant state induced by decreasing E-cadherin function was associated with and required an approximately two to threefold decrease in RalA expression. Moreover, direct knockdown of RalA to a similar degree by shRNA expression in these cells reduced E-cadherin levels and also induced progression to a malignant phenotype. Knockdown of the Ral effector, Exo84, mimicked the effects of decreasing RalA levels in these engineered tissues. These phenomena can be explained by our finding that the stability of E-cadherin in Ras-expressing keratinocytes depends upon this RalA signaling cascade. These results imply that an important component of the early stages in squamous carcinoma progression may be a modest decrease in RalA gene expression that magnifies the effects of decreased E-cadherin expression by promoting its degradation.

Indexed as

AnimalsBlotting, WesternCadherinsCarcinoma, Squamous CellCell Culture TechniquesCell LineCells, CulturedCell Transformation, NeoplasticDisease ProgressionHumansImmunohistochemistryKeratinocytesMaleMiceMice, NudeNeoplasm StagingCadherinsEXOC8 protein, humanRALA protein, humanral GTP-Binding Proteinsras ProteinsVesicular Transport Proteins

Identifiers

PMID19802010
PMCPMC2803332
OpenAlexW2064212866

What Socratic 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 Socratic graph.