Evidence map›Paper›PMID 33830081›Full record

ArticleJCI insight2021

Selective targeting of KRAS-driven lung tumorigenesis via unresolved ER stress.

Iwao Shimomura, Naoaki Watanabe, Tomofumi Yamamoto, Minami Kumazaki, Yuji Tada, Koichiro Tatsumi, Takahiro Ochiya, Yusuke Yamamoto

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

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 54% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. 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

8 authors at 2 institutions in 1 country.

Iwao ShimomuraDivision of Cellular Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Naoaki WatanabeDivision of Cellular Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Tomofumi YamamotoDivision of Cellular Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Minami KumazakiDivision of Cellular Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Yuji TadaDepartment of Respirology, Graduate School of Medicine, Chiba University, Chuo-ku Chiba-shi, Chiba, Japan.
Koichiro TatsumiDepartment of Respirology, Graduate School of Medicine, Chiba University, Chuo-ku Chiba-shi, Chiba, Japan.
Takahiro OchiyaDepartment of Molecular and Cellular Medicine, Institute of Medical Science, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
Yusuke YamamotoDivision of Cellular Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
Chiba University · JPTokyo Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lung cancer with oncogenic KRAS makes up a significant proportion of lung cancers and is accompanied by a poor prognosis. Recent advances in understanding the molecular pathogenesis of lung cancer with oncogenic KRAS have enabled the development of drugs, yet mutated KRAS remains undruggable. We performed small-molecule library screening and identified verteporfin, a yes-associated protein 1 (YAP1) inhibitor; verteporfin treatment markedly reduced cell viability in KRAS-mutant lung cancer cells in vitro and suppressed KRAS-driven lung tumorigenesis in vivo. Comparative functional analysis of verteporfin treatment and YAP1 knockdown with siRNA revealed that the cytotoxic effect of verteporfin was at least partially independent of YAP1 inhibition. A whole-transcriptome approach revealed the distinct expression profiles in KRAS-mutant lung cancer cells between verteporfin treatment and YAP1 knockdown and identified the selective involvement of the ER stress pathway in the effects of verteporfin treatment in KRAS-mutant lung cancer, leading to apoptotic cell death. These data provide novel insight to uncover vulnerabilities in KRAS-driven lung tumorigenesis.

Indexed as

AnimalsAntineoplastic AgentsApoptosisEndoplasmic Reticulum StressFemaleGene Expression Regulation, NeoplasticHumansLung NeoplasmsMiceMice, Inbred BALB CMutationProto-Oncogene Proteins p21(ras)VerteporfinXenograft Model Antitumor AssaysYAP-Signaling ProteinsAntineoplastic AgentsKRAS protein, humanProto-Oncogene Proteins p21(ras)VerteporfinYAP1 protein, humanYAP-Signaling ProteinsCell BiologyDrug screensLung cancerOncogenesOncology

Identifiers

PMID33830081
PMCPMC8119185
OpenAlexW3144492700

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.