Evidence map›Paper›PMID 31623313›Full record

ArticleCancers2019

CRISPR-Cas9 Knockdown and Induced Expression of CD133 Reveal Essential Roles in Melanoma Invasion and Metastasis.

Cynthia M Simbulan-Rosenthal, Ryan Dougherty, Sahar Vakili, Alexandra M Ferraro, Li-Wei Kuo, Ryyan Alobaidi, Leala Aljehane, Anirudh Gaur, Peter Sykora, Eric Glasgow and 2 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.1field-weighted citation impact, top 11% 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

24 citing papers in PubMed, 35 citations in OpenAlex.

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  20. Benefits of Zebrafish Xenograft Models in Cancer Research.Frontiers in cell and developmental biology · 2021
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Cynthia M Simbulan-RosenthalDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20007, USA. simbulac@georgetown.edu.ORCID 0000-0002-5070-0342
Ryan DoughertyDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20007, USA. rdd40@georgetown.edu.ORCID 0000-0002-0330-0119
Sahar VakiliDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20007, USA. sv457@georgetown.edu.
Alexandra M FerraroDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20007, USA. amf315@georgetown.edu.
Li-Wei KuoDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20007, USA. lk702@georgetown.edu.
Ryyan AlobaidiDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20007, USA. raa125@georgetown.edu.
Leala AljehaneDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20007, USA. la591@georgetown.edu.
Anirudh GaurDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20007, USA. ag854@georgetown.edu.
Peter SykoraAmelia Technologies, Rockville, MD 20850, USA. peters@ameliatechnologies.com.
Eric GlasgowDepartment of Oncology, Georgetown University School of Medicine, Washington, DC 20007, USA. eg239@georgetown.edu.
Seema AgarwalDepartment of Pathology, Georgetown University School of Medicine, Washington, DC 20007, USA. Seema.Agarwal@georgetown.edu.
Dean S RosenthalDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University School of Medicine, Washington, DC 20007, USA. rosenthd@georgetown.edu.ORCID 0000-0002-7624-0209
Georgetown University · US

Funding

Immuno-CometChip for Human Skin Basal Cell Genotoxicity TestingR42ES026908 · NIEHS · AMELIA TECHNOLOGIES, LLC · PI GEORGE, JAY, ROSENTHAL, DEAN · 2018 to 2019
$1.5M
NIEHS NIH HHS 5 R42 ES026908 03
6 · The paper itself

Abstract

CD133, known as prominin1, is a penta-span transmembrane glycoprotein presumably a cancer stem cell marker for carcinomas, glioblastomas, and melanomas. We showed that CD133(+) 'melanoma-initiating cells' are associated with chemoresistance, contributing to poor patient outcome. The current study investigates the role(s) of CD133 in invasion and metastasis. Magnetic-activated cell sorting of a melanoma cell line (BAKP) followed by transwell invasion assays revealed that CD133(+) cells are significantly more invasive than CD133(-) cells. Conditional reprogramming of BAKP CD133(+) cells maintained stable CD133 overexpression (BAK-R), and induced cancer stem cell markers, melanosphere formation, and chemoresistance to kinase inhibitors. BAK-R cells showed upregulated CD133 expression, and consequently were more invasive and metastatic than BAK-P cells in transwell and zebrafish assays. CD133 knockdown by siRNA or CRISPR-Cas9 (BAK-R-T3) in BAK-R cells reduced invasion and levels of matrix metalloproteinases MMP2/MMP9. BAK-R-SC cells, but not BAK-R-T3, were metastatic in zebrafish. While CD133 knockdown by siRNA or CRISPR-Cas9 in BAK-P cells attenuated invasion and diminished MMP2/MMP9 levels, doxycycline-induced CD133 expression in BAK-P cells enhanced invasion and MMP2/MMP9 concentrations. CD133 may therefore play an essential role in invasion and metastasis via upregulation of MMP2/MMP9, leading to tumor progression, and represents an attractive target for intervention in melanoma.

Indexed as

CRISPR-Cas9 knockdowninvasionmatrix metalloproteinasesmelanoma initiating cellsmetastasis

Identifiers

PMID31623313
PMCPMC6827046
OpenAlexW2978073812

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.