Evidence map›Paper›PMID 26148233›Full record

ArticleOncogene2016

Regulation of complement-dependent cytotoxicity by TGF-β-induced epithelial-mesenchymal transition.

M T Goswami, A K Reka, H Kurapati, V Kaza, J Chen, T J Standiford, V G Keshamouni

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.9field-weighted citation impact, top 9% 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

33 citing papers in PubMed, 54 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

7 authors at 1 institution in 1 country.

M T GoswamiDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
A K RekaDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
H KurapatiDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
V KazaDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
J ChenDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
T J StandifordDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
V G KeshamouniDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI, USA.
University of Michigan–Ann Arbor · US

Funding

Novel IL-1 Family Members in Lung Innate ImmunityR01HL123515 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI STANDIFORD, THEODORE J. · 2015 to 2018
$2.5M
Flagellin Stimulates Lung Innate Mucosal ImmunityR01HL097564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI STANDIFORD, THEODORE J. · 2010 to 2013
$1.7M
Regulation of Tumor Associated Macrophages by TGF-betaR01CA132571 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KESHAMOUNI, VENKATESHWAR G · 2008 to 2012
$1.4M
NCI NIH HHS CA132571-01NCI NIH HHS R01 CA132571NHLBI NIH HHS R01 HL097564NHLBI NIH HHS R01 HL123515PHS HHS NIH/NHLBI HL097564
6 · The paper itself

Abstract

The process of epithelial-mesenchymal transition (EMT), in addition to being an initiating event for tumor metastasis, is implicated in conferring several clinically relevant properties to disseminating cancer cells. These include stem cell-like properties, resistance to targeted therapies and ability to evade immune surveillance. Enrichment analysis of gene expression changes during transforming growth factor-β (TGF-β)-induced EMT in lung cancer cells identified complement cascade as one of the significantly enriched pathway. Further analysis of the genes in the complement pathway revealed an increase in the expression of complement inhibitors and a decrease in the expression of proteins essential for complement activity. In this study, we tested whether EMT confers resistance to complement-dependent cytotoxicity (CDC) in lung cancer cells and promotes tumor progression. CD59 is a potent inhibitor of membrane attack complex that mediates complement-dependent cell lysis. We observed a significant increase in the CD59 expression on the surface of cells after TGF-β-induced EMT. Furthermore, CD59 knockdown restored susceptibility of cells undergoing EMT to cetuximab-mediated CDC. TGF-β-induced CD59 expression during EMT is dependent on Smad3 but not on Smad2. Chromatin immunoprecipitation analysis confirmed that Smad3 directly binds to the CD59 promoter. Stable knockdown of CD59 in A549 cells inhibited experimental metastasis. These results demonstrate that TGF-β-induced EMT and CD59 expression confers an immune-evasive mechanism to disseminating tumor cells facilitating tumor progression. Together, our data demonstrates that CD59 inhibition may serve as an adjuvant to enhance the efficacy of antibody-mediated therapies, as well as to inhibit metastasis in lung cancer.

Indexed as

Complement ActivationAdenocarcinomaAnimalsCD59 AntigensCell Line, TumorCetuximabComplement Membrane Attack ComplexCytotoxicity, ImmunologicEpithelial-Mesenchymal TransitionGene Expression Regulation, NeoplasticGenetic VectorsHumansIntracellular Signaling Peptides and ProteinsLung NeoplasmsMaleMiceCD59 AntigensCD59 protein, humanCetuximabComplement Membrane Attack ComplexIntracellular Signaling Peptides and ProteinsLyst protein, mouseNeoplasm ProteinsProteinsRNA, MessengerRNA, NeoplasmRNA, Small InterferingSmad3 ProteinSMAD3 protein, humanTransforming Growth Factor betaVesicular Transport Proteins

Identifiers

PMID26148233
PMCPMC4703565
OpenAlexW1536072591

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.