Evidence map›Paper›PMID 34751028›Full record

ArticleJournal of proteome research2021

Cholesterol Regulates the Tumor Adaptive Resistance to MAPK Pathway Inhibition.

Xu-Dong Wang, Chiho Kim, Yajie Zhang, Smita Rindhe, Melanie H Cobb, Yonghao Yu

Open access · greenAbstract read
In one paragraph

Article in Journal of proteome research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.6field-weighted citation impact, top 35% 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

11 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
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  4. Decoding the Role of Lipid Metabolism and Membrane Dynamics in Melanoma.International journal of molecular sciences · 2026
    Review
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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

6 authors at 1 institution in 1 country.

Xu-Dong WangDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, 75390 Texas, United States.
Chiho KimDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, 75390 Texas, United States.
Yajie ZhangDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, 75390 Texas, United States.
Smita RindheDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, 75390 Texas, United States.
Melanie H CobbSimmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, 75390 Texas, United States.ORCID 0000-0003-0833-5473
Yonghao YuDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, 75390 Texas, United States.ORCID 0000-0001-8414-4666
The University of Texas Southwestern Medical Center · US

Funding

TRAFFICKING AND ABETA AGGREGATIONP01AG031097 · NIA · SCRIPPS RESEARCH INSTITUTE, THE · PI KELLY, JEFFERY W · 2009 to 2013
$10.2M
Posttranslational Regulation of Cell Growth and Stress ResponsesR35GM134883 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI YU, YONGHAO · 2020 to 2024
$2.7M
Molecular and Biochemical Basis of mTORC1-mediated Feedback LoopsR01GM114160 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI YU, YONGHAO · 2015 to 2019
$1.6M
Laser Scanning Confocal for UT Southwestern Live Cell Imaging FacilityS10OD021684 · OD · UT SOUTHWESTERN MEDICAL CENTER · PI LUBY-PHELPS, KATHERINE J · 2016 to 2016
$455k
NIA NIH HHS P01 AG031097NIGMS NIH HHS R01 GM114160NIGMS NIH HHS R35 GM134883NIH HHS S10 OD021684
6 · The paper itself

Abstract

Although targeted MAPK pathway inhibition has achieved remarkable patient responses in many cancers, the development of resistance has remained a critical challenge. Adaptive tumor response underlies the drug resistance. Furthermore, such bypass mechanisms often lead to the activation of many pro-survival kinases, which complicates the rational design of combination therapies. Here, we performed global tyrosine phosphoproteomic (pTyr) analyses and demonstrated that targeted MAPK signaling inhibition in melanoma leads to a profound remodeling of the pTyr proteome. Intriguingly, altered cholesterol metabolism might drive, in a coordinated fashion, the activation of these kinases. Indeed, we found an accumulation of intracellular cholesterol in melanoma cells (with BRAF

Indexed as

Carcinoma, Non-Small-Cell LungLung NeoplasmsMelanomaCell Line, TumorCholesterolHumansMAP Kinase Signaling SystemMutationProtein Kinase InhibitorsProto-Oncogene Proteins B-rafCholesterolProtein Kinase InhibitorsProto-Oncogene Proteins B-rafadaptive resistancecholesterolcombination treatmentphosphoproteomicRTK

Identifiers

PMID34751028
PMCPMC8905657
OpenAlexW3212839014

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.