Evidence map›Paper›PMID 25886575›Full record

ArticleBMC cancer2015

Induction of tumor initiation is dependent on CD44s in c-Met⁺ hepatocellular carcinoma.

Hien Dang, Steven N Steinway, Wei Ding, Carl B Rountree

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

Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

20 citing papers in PubMed, 27 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

4 authors at 1 institution in 1 country.

Hien DangDepartment of Pediatrics and Pharmacology, The Pennsylvania State University, College of Medicine, Penn State Children's Hospital, Hershey, PA, USA. danghi@mail.nih.gov.
Steven N SteinwayDepartment of Pediatrics and Pharmacology, The Pennsylvania State University, College of Medicine, Penn State Children's Hospital, Hershey, PA, USA. ssteinway@hmc.psu.edu.
Wei DingDepartment of Pediatrics and Pharmacology, The Pennsylvania State University, College of Medicine, Penn State Children's Hospital, Hershey, PA, USA. wud1@psu.edu.
Carl B RountreeDepartment of Pediatrics and Pharmacology, The Pennsylvania State University, College of Medicine, Penn State Children's Hospital, Hershey, PA, USA. carl_rountree@bshsi.org.
Penn State Milton S. Hershey Medical Center · US

Funding

Mechanisms of survival of liver cancer stem cellsR03DK088013 · NIDDK · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI ROUNTREE, CARL BARTH · 2010 to 2011
$154k
Network modeling of epithelial mesenchymal transition in liver cancer metastasisF30DK093234 · NIDDK · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI STEINWAY, STEVEN N. · 2011 to 2015
$137k
NIDDK NIH HHS 1F30DK093234-01NIDDK NIH HHS F30 DK093234NIDDK NIH HHS R03 DK088013NIDDK NIH HHS R03DK088013
6 · The paper itself

Abstract

backgroundHepatocellular carcinoma (HCC) patients with active hepatocyte growth factor (HGF)/c-Met signaling have a significantly worse prognosis. c-Met, a high affinity receptor for HGF, plays a critical role in cancer growth, invasion and metastasis. c-Met and CD44 have been utilized as cell surface markers to identify mesenchymal tumor-initiating stem-like cells (TISC) in several cancers including HCC. In this work, we examine the complex relationship between c-Met and CD44s (standard form), and investigate the specific role of CD44s as a tumor initiator and stemness marker in HCC.

methodsGene and protein expression assays were utilized to investigate the relationship between CD44s and c-Met in HCC cell lines. Tumor-sphere assays and in vivo tumor assays were performed to investigate the role of CD44+ cells as TISCs. Student's t-test or one-way ANOVA with Tukeys post-hoc test was performed to test for differences amongst groups with a p < .05 as significant.

resultsIn an immunohistochemical and immunoblot analysis of human HCC samples, we observed that more than 39% of human HCC samples express c-Met and CD44. To study the relationship between c-Met and CD44, we used MHCC97-H cells, which are CD44(+)/c-Met(+). The knockdown of c-Met in MHCC97-H cells decreased CD44s, reduced TISC characteristics and decreased tumorsphere formation. Furthermore, we demonstrate that the inhibition of PI3K/AKT signaling decreased CD44s expression and subsequently decreased tumorsphere formation. The down-regulation of CD44s leads to a significant loss of a TISC and mesenchymal phenotype. Finally, the down-regulation of CD44s in MHCC97-H cells decreased tumor initiation in vivo compared with the scrambled control.

conclusionsIn summary, our data suggest that CD44s is modulated by the c-Met-PI3K-AKT signaling cascade to support a mesenchymal and TISC phenotype in HCC cells. Moreover, c-Met could be a potential therapeutic drug for targeting HCC cells with TISC and mesenchymal phenotypes.

Indexed as

AnimalsCarcinoma, HepatocellularCell Line, TumorCell Transformation, NeoplasticHumansHyaluronan ReceptorsLiver NeoplasmsMiceMice, NudeNeoplastic Stem CellsReceptor Protein-Tyrosine KinasesCD44S antigenHyaluronan ReceptorsReceptor Protein-Tyrosine KinasesRON protein

Identifiers

PMID25886575
PMCPMC4380258
OpenAlexW2129237207

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.