Evidence map›Paper›PMID 17982486›Full record

ArticleOncogene2008

Synergistic effect between EGF and TGF-beta1 in inducing oncogenic properties of intestinal epithelial cells.

S Uttamsingh, X Bao, K T Nguyen, M Bhanot, J Gong, J L-K Chan, F Liu, T T Chu, L-H Wang

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 7% 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

82 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.

  1. Pooled it
  2. Review
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  12. Review
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  18. Article
  19. Review
  20. Paradoxical Roles of Leucine-Rich αFrontiers in cell and developmental biology · 2021
    Article

22 more citing papers are in PubMed but not listed here.

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

9 authors at 3 institutions in 1 country.

S UttamsinghDepartment of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
X Bao
K T Nguyen
M Bhanot
J Gong
J L-K Chan
F Liu
T T Chu
L-H Wang
Icahn School of Medicine at Mount Sinai · USRutgers, The State University of New Jersey · USUniversity of Michigan–Ann Arbor · US

Funding

TRANSFORMING GENES OF AVIAN SARCOMA VIRUSESR01CA029339 · NCI · ROCKEFELLER UNIVERSITY · PI WANG, LU-HAI · 1985 to 2006
$2.3M
CELL TRANSFORMATION BY INSULIN AND IGFI RECEPTORSR01CA055054 · NCI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI WANG, LU-HAI · 1992 to 2002
$870k
NCI NIH HHS CA29339NCI NIH HHS CA55054
6 · The paper itself

Abstract

Transforming growth factor (TGF)-beta1 has a biphasic effect on rat intestinal epithelial (RIE) cells. By itself, TGF-beta1 functions as a tumor suppressor by inhibiting the growth, migration and invasion of RIE cells. We show in this study that in conjunction with epidermal growth factor (EGF), TGF-beta1 helped to augment migration, invasion and anchorage-independent growth (AIG) compared to that by EGF alone. EGF plus TGF-beta1 induced a dramatic morphological change characteristic of epithelial-mesenchymal transition (EMT). The mechanism for this enhanced effect of TGF-beta1 and EGF on oncogenic properties was explored by analysis of EGF- and TGF-beta1-mediated signaling pathways and complementary DNA arrays. TGF-beta1 augmented EGF-mediated signaling of mitogen-activated protein kinase (MAPK) and AKT by enhancing and prolonging the activation of the former and prolonging the activation of the latter. Inhibition of MAPK, but not phosphoinositide-3 kinase (PI3K), abolished TGF-beta1 plus EGF-induced EMT and downregulation of E-cadherin at mRNA and protein levels. By contrast, cell migration and invasion were sensitive to inhibition of either MAPK or PI3 kinase. TGF-beta1 plus EGF-induced AIG was significantly more resistant to inhibition of PI3K and MAPK compared to that induced by EGF alone. EGF and TGF-beta1 synergistically induced the expression of a series of proteases including matrix metalloproteinase (MMP) 1 (collagenase), MMP3, MMP9, MMP10, MMP14 and cathepsin. Among them, the expression of MMP1, MMP3, MMP9 and MMP10 was MAPK dependent. Inhibition of the MMPs or cathepsin significantly blocked EGF plus TGF-beta1-induced invasion, but had no effect on colony formation. Phospholipase C (PLC) and Cox2 induced by EGF plus TGF-beta1 also played a significant role in invasion, whereas PLC was also important for colony formation. Our study reveals specific signaling functions and induction of genes differentially required for enhanced effect of EGF- and TGF-beta1-induced oncogenic properties, and helps to explain the tumor-promoting effect of TGF-beta1 in human cancer with elevated expression or activation of TGF-beta1 and receptor protein tyrosine kinases.

Indexed as

AnimalsCathepsinsCell MovementCell ProliferationCell Transformation, NeoplasticDrug SynergismEpidermal Growth FactorEpithelial CellsExtracellular Signal-Regulated MAP KinasesGene Expression ProfilingHumansIntestinal MucosaMatrix Metalloproteinase InhibitorsMatrix MetalloproteinasesOligonucleotide Array Sequence AnalysisPhosphatidylinositol 3-KinasesCathepsinsEpidermal Growth FactorExtracellular Signal-Regulated MAP KinasesMatrix Metalloproteinase InhibitorsMatrix MetalloproteinasesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTransforming Growth Factor beta1Tumor Suppressor ProteinsType C Phospholipases

Identifiers

PMID17982486
OpenAlexW1970687486

What OpenQuestion holds

Textmetadata
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.