Evidence map›Paper›PMID 32499517›Full record

ArticleScientific reports2020

Avicin G is a potent sphingomyelinase inhibitor and blocks oncogenic K- and H-Ras signaling.

Christian M Garrido, Karen M Henkels, Kristen M Rehl, Hong Liang, Yong Zhou, Jordan U Gutterman, Kwang-Jin Cho

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

10 citing papers in PubMed, 18 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 3 institutions in 1 country.

Christian M GarridoDepartment of Biochemistry and Molecular Biology, School of Boonshoft Medical School, Wright State University, Dayton, OH, 45435, United States.
Karen M HenkelsDepartment of Biochemistry and Molecular Biology, School of Boonshoft Medical School, Wright State University, Dayton, OH, 45435, United States.
Kristen M RehlDepartment of Biochemistry and Molecular Biology, School of Boonshoft Medical School, Wright State University, Dayton, OH, 45435, United States.
Hong LiangDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, United States.
Yong ZhouDepartment of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, 77030, United States.
Jordan U GuttermanDepartment of Systems Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, United States.
Kwang-Jin ChoDepartment of Biochemistry and Molecular Biology, School of Boonshoft Medical School, Wright State University, Dayton, OH, 45435, United States. kwang-jin.cho@wright.edu.
Wright State University · USThe University of Texas Health Science Center at Houston · USThe University of Texas MD Anderson Cancer Center · US

Funding

K-Ras plasma membrane interactions: a tractable therapeutic targetR00CA188593 · NCI · WRIGHT STATE UNIVERSITY · PI CHO, KWANGJIN · 2017 to 2019
$747k
NCI NIH HHS R00 CA188593
6 · The paper itself

Abstract

K-Ras must interact primarily with the plasma membrane (PM) for its biological activity. Therefore, disrupting K-Ras PM interaction is a tractable approach to block oncogenic K-Ras activity. Here, we found that avicin G, a family of natural plant-derived triterpenoid saponins from Acacia victoriae, mislocalizes K-Ras from the PM and disrupts PM spatial organization of oncogenic K-Ras and H-Ras by depleting phosphatidylserine (PtdSer) and cholesterol contents, respectively,  at the inner PM leaflet. Avicin G also inhibits oncogenic K- and H-Ras signal output and the growth of K-Ras-addicted pancreatic and non-small cell lung cancer cells. We further identified that avicin G perturbs lysosomal activity, and disrupts cellular localization and activity of neutral and acid sphingomyelinases (SMases), resulting in elevated cellular sphingomyelin (SM) levels and altered SM distribution. Moreover, we show that neutral SMase inhibitors disrupt the PM localization of K-Ras and PtdSer and oncogenic K-Ras signaling. In sum, this study identifies avicin G as a new potent anti-Ras inhibitor, and suggests that neutral SMase can be a tractable target for developing anti-K-Ras therapeutics.

Indexed as

AnimalsCell LineCell MembraneCholesterolCricetinaeDogsEndocytosisHumansras ProteinsSaponinsSignal TransductionSphingomyelin PhosphodiesteraseSphingomyelinsavicin GCholesterolras ProteinsSaponinsSphingomyelin PhosphodiesteraseSphingomyelins

Identifiers

PMID32499517
PMCPMC7272413
OpenAlexW3033470551

What OpenQuestion holds

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LicenceCC BY
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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.