Evidence map›Paper›PMID 31461647›Full record

ArticleCell reports2019

TRPML1 Promotes Protein Homeostasis in Melanoma Cells by Negatively Regulating MAPK and mTORC1 Signaling.

Stacy Y Kasitinon, Ugur Eskiocak, Misty Martin, Divya Bezwada, Vishal Khivansara, Alpaslan Tasdogan, Zhiyu Zhao, Thomas Mathews, Arin B Aurora, Sean J Morrison

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

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

38 citing papers in PubMed, 51 citations in OpenAlex.

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  17. Lysosomal Potassium Channels.Handbook of experimental pharmacology · 2023
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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

10 authors at 2 institutions in 1 country.

Stacy Y KasitinonChildren's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Ugur EskiocakChildren's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Misty MartinChildren's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Divya BezwadaChildren's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Vishal KhivansaraChildren's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Alpaslan TasdoganChildren's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Zhiyu ZhaoChildren's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Thomas MathewsChildren's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Arin B AuroraChildren's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Sean J MorrisonChildren's Research Institute and Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: sean.morrison@utsouthwestern.edu.
The University of Texas Southwestern Medical Center · USHoward Hughes Medical Institute · US

Funding

L-type Calcium Channels as PotentialTherapeutic Targets for MelanomaF30CA216885 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI YUAN, WEN-CHENG STACY · 2017 to 2019
$114k
Dissecting Fatty Acid Metabolism in Clear Cell Renal Cell Carcinoma (ccRCC)F31CA239330 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI BEZWADA, DIVYA · 2019 to 2021
$103k
Howard Hughes Medical InstituteNCI NIH HHS F30 CA216885NCI NIH HHS F31 CA239330
6 · The paper itself

Abstract

We screen ion channels and transporters throughout the genome to identify those required by human melanoma cells but not by normal human melanocytes. We discover that Mucolipin-1 (MCOLN1), which encodes the lysosomal cation channel TRPML1, is preferentially required for the survival and proliferation of melanoma cells. Loss of MCOLN1/TRPML1 function impairs the growth of patient-derived melanomas in culture and in xenografts but does not affect the growth of human melanocytes. TRPML1 expression and macropinocytosis are elevated in melanoma cells relative to melanocytes. TRPML1 is required in melanoma cells to negatively regulate MAPK pathway and mTORC1 signaling. TRPML1-deficient melanoma cells exhibit decreased survival, proliferation, tumor growth, and macropinocytosis, as well as serine depletion and proteotoxic stress. All of these phenotypes are partially or completely rescued by mTORC1 inhibition. Melanoma cells thus increase TRPML1 expression relative to melanocytes to attenuate MAPK and mTORC1 signaling, to sustain macropinocytosis, and to avoid proteotoxic stress.

Indexed as

MAP Kinase Signaling SystemProteostasisAnimalsCell Line, TumorCell ProliferationFemaleHumansMaleMechanistic Target of Rapamycin Complex 1MelanomaMicePhenotypePinocytosisTransient Receptor Potential ChannelsTumor Cells, CulturedMCOLN1 protein, humanMechanistic Target of Rapamycin Complex 1Transient Receptor Potential Channelsion channelmacropinocytosisMAPKMCOLN1melanomamTORproteostasissignalingTRPML1

Identifiers

PMID31461647
PMCPMC6813770
OpenAlexW2970652230

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.