Evidence map›Paper›PMID 27390927›Full record

ArticleBMC cancer2016

Coalition of Oct4A and β1 integrins in facilitating metastasis in ovarian cancer.

Chantel Samardzija, Rodney B Luwor, Michael A Quinn, George Kannourakis, Jock K Findlay, Nuzhat Ahmed

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

Article in BMC cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.9field-weighted citation impact, top 26% 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

5 citing papers in PubMed, 9 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

6 authors at 3 institutions in 1 country.

Chantel SamardzijaDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Melbourne, VIC, 3052, Australia.
Rodney B LuworDepartment of Surgery, University of Melbourne, Parkville, Melbourne, VIC, 3052, Australia.
Michael A QuinnDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Melbourne, VIC, 3052, Australia.
George KannourakisFiona Elsey Cancer Research Institute, Suites 23-26, 106-110 Lydiard Street South, Ballarat Technology Central Park, Ballarat, 3353, Australia.
Jock K FindlayDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Melbourne, VIC, 3052, Australia.
Nuzhat AhmedDepartment of Obstetrics and Gynaecology, University of Melbourne, Parkville, Melbourne, VIC, 3052, Australia. nuzhata@unimelb.edu.au.
University of Melbourne · AUFederation University · AUHudson Institute of Medical Research · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOvarian cancer is a metastatic disease and one of the leading causes of gynaecology malignancy-related deaths in women. Cancer stem cells (CSCs) are key contributors of cancer metastasis and relapse. Integrins are a family of cell surface receptors which allow interactions between cells and their surrounding microenvironment and play a fundamental role in promoting metastasis. This study investigates the molecular mechanism which associates CSCs and integrins in ovarian cancer metastasis.

methodsThe expression of Oct4A in high-grade serous ovarian tumors and normal ovaries was determined by immunofluorescence analysis. The functional role of Oct4A was evaluated by generating stable knockdown (KD) of Oct4A clones in an established ovarian cancer cell line HEY using shRNA-mediated silencing. The expression of integrins in cell lines was evaluated by flow cytometry. Spheroid forming ability, adhesion and the activities of matrix metalloproteinases 9/2 (MMP-9/2) was measured by in vitro functional assays and gelatin zymography. These observations were further validated in in vivo mouse models using Balb/c nu/nu mice.

resultsWe report significantly elevated expression of Oct4A in high-grade serous ovarian tumors compared to normal ovarian tissues. The expression of Oct4A in ovarian cancer cell lines correlated with their CSC-related sphere forming abilities. The suppression of Oct4A in HEY cells resulted in a significant diminution of integrin β1 expression and associated α5 and α2 subunits compared to vector control cells. This was associated with a reduced adhesive ability on collagen and fibronectin and decreased secretion of pro-MMP2 in Oct4A KD cells compared to vector control cells. In vivo, Oct4A knock down (KD) cells produced tumors which were significantly smaller in size and weight compared to tumors derived from vector control cells. Immunohistochemical analyses of Oct4A KD tumor xenografts demonstrated a significant loss of cytokeratin 7 (CK7), Glut-1 as well as CD34 and CD31 compared to vector control cell-derived xenografts.

conclusionThe expression of Oct4A may be crucial to promote and sustain integrin-mediated extracellular matrix (ECM) remodeling requisite for tumor metastasis in ovarian cancer patients.

Indexed as

AnimalsCell AdhesionCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansIntegrin alpha ChainsIntegrin beta1Matrix Metalloproteinase 2Matrix Metalloproteinase 9Mice, Inbred BALB CMice, NudeNeoplasms, Cystic, Mucinous, and SerousNeoplasm TransplantationOctamer Transcription Factor-3Ovarian NeoplasmsIntegrin alpha ChainsIntegrin beta1Matrix Metalloproteinase 2Matrix Metalloproteinase 9MMP2 protein, humanMMP9 protein, humanOctamer Transcription Factor-3POU5F1 protein, humanProtein IsoformsCancer stem cellsChemoresistanceIntegrinsMetastasisOct4AOvarian carcinomaRecurrence

Identifiers

PMID27390927
PMCPMC4939035
OpenAlexW2468147905

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.