Evidence map›Paper›PMID 29896883›Full record

ArticleMolecular oncology2018

Macrophage migration inhibitory factor promotes resistance to MEK blockade in KRAS mutant colorectal cancer cells.

Seul-Ki Cheon, Hwang-Phill Kim, Ye-Lim Park, Jee-Eun Jang, Yoojoo Lim, Sang-Hyun Song, Sae-Won Han, Tae-You Kim

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

Article in Molecular oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

12 citing papers in PubMed, 17 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

8 authors at 2 institutions in 1 country.

Seul-Ki CheonDepartment of Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Korea.
Hwang-Phill KimDepartment of Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Korea.
Ye-Lim ParkDepartment of Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Korea.
Jee-Eun JangCancer Research Institute, Seoul National University, Korea.
Yoojoo LimDepartment of Internal Medicine, Seoul National University Hospital, Korea.
Sang-Hyun SongCancer Research Institute, Seoul National University, Korea.
Sae-Won HanCancer Research Institute, Seoul National University, Korea.
Tae-You KimDepartment of Molecular Medicine & Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Korea.
Seoul National University · KRSeoul National University Hospital · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although MEK blockade has been highlighted as a promising antitumor drug, it has poor clinical efficacy in KRAS mutant colorectal cancer (CRC). Several feedback systems have been described in which inhibition of one intracellular pathway leads to activation of a parallel signaling pathway, thereby decreasing the effectiveness of single-MEK targeted therapies. Here, we investigated a bypass mechanism of resistance to MEK inhibition in KRAS CRC. We found that KRAS mutant CRC cells with refametinib, MEK inhibitor, induced MIF secretion and resulted in activation of STAT3 and MAPK. MIF knockdown by siRNA restored sensitivity to refametinib in KRAS mutant cells. In addition, combination with refametinib and 4-IPP, a MIF inhibitor, effectively reduced the activity of STAT3 and MAPK, more than single-agent treatment. As a result, combined therapy was found to exhibit a synergistic growth inhibitory effect against refametinib-resistant cells by inhibition of MIF activation. These results reveal that MIF-induced STAT3 and MAPK activation evoked an intrinsic resistance to refametinib. Our results provide the basis for a rational combination strategy against KRAS mutant colorectal cancers, predicated on the understanding of cross talk between the MEK and MIF pathways.

Indexed as

ApoptosisCell Line, TumorColorectal NeoplasmsDiphenylamineDrug Resistance, NeoplasmHumansIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMAP Kinase Signaling SystemMitogen-Activated Protein KinasesMutationProtein Kinase InhibitorsProto-Oncogene Proteins p21(ras)RNA InterferenceRNA, Small InterferingSulfonamidesDiphenylamineIntramolecular OxidoreductasesKRAS protein, humanMacrophage Migration-Inhibitory FactorsMIF protein, humanMitogen-Activated Protein KinasesN-(3,4-difluoro-2-(2-fluoro-4-iodophenylamino)-6-methoxyphenyl)-1-(2,3-dihydroxypropyl)cyclopropane-1-sulfonamideProtein Kinase InhibitorsProto-Oncogene Proteins p21(ras)RNA, Small InterferingSulfonamidescolorectal cancerfeedback mechanismKRASMIFrefametinib

Identifiers

PMID29896883
PMCPMC6068346
OpenAlexW2807742933

What OpenQuestion holds

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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.