Evidence map›Paper›PMID 30467396›Full record

ArticleScientific reports2018

Effects of Modulating Actin Dynamics on HER2 Cancer Cell Motility and Metastasis.

Sarah Nersesian, Rodette Williams, Daniel Newsted, Kavan Shah, Stephanie Young, P Andrew Evans, John S Allingham, Andrew W Craig

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. 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
1.2field-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

11 citing papers in PubMed, 19 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

8 authors at 1 institution in 1 country.

Sarah NersesianDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Rodette WilliamsDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Daniel NewstedDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Kavan ShahDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Stephanie YoungDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
P Andrew EvansDepartment of Chemistry, Queen's University, Kingston, Ontario, Canada.ORCID http://orcid.org/0000-0001-6609-5282
John S AllinghamDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada.
Andrew W CraigDepartment of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada. andrew.craig@queensu.ca.ORCID http://orcid.org/0000-0002-2039-2393
Queen's University · CA

Funding

Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada) 134763Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada) 151976
6 · The paper itself

Abstract

Amplification of HER2 leads to development of HER2-positive (HER2+) cancers with high rates of metastasis compared to other cancer subtypes. The goal of this study was to probe the vulnerability of HER2+ cancer cells to a filamentous actin (F-actin) severing and capping toxin. The growth and viability of human HER2+ breast cancer (HCC1954) and ovarian cancer (SKOV3) cell lines were significantly impaired upon treatment with the marine macrolide mycalolide B (Myc B) at doses above 100 nanomolar. Further testing of Myc B in combination with the antibody-drug conjugate Trastuzumab-emtansine (T-DM1) led to improved killing of SKOV3 cells compared to either treatment alone. At sub-lethal doses, treatment of HER2+ cancer cells with Myc B resulted in rapid loss of leading edge protrusions and formation of aggresomes containing F-actin and the actin regulatory protein Cortactin. This correlated with robust inhibition of HER2+ cancer cell motility and invasion with Myc B treatment. In SKOV3 tumor xenograft assays, intratumoral injections of Myc B impaired HER2+ tumor growth and metastasis, with maximal effects observed in combination with systemic delivery of Trastuzumab. Metastasis of SKOV3 cells to the lungs following tail vein injection was also reduced by Myc B. Together, these findings provide rationale for targeting F-actin in combination with existing therapies for HER2+ cancers to reduce metastasis.

Indexed as

Ado-Trastuzumab EmtansineAnimalsBreast NeoplasmsCell Line, TumorCell MovementCell ProliferationCell SurvivalDrug SynergismErb-b2 Receptor Tyrosine KinasesFemaleHumansLung NeoplasmsMarine ToxinsMaytansineMiceOvarian NeoplasmsAdo-Trastuzumab EmtansineERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesMarine ToxinsMaytansinemycalolide BOxazolesTrastuzumab

Identifiers

PMID30467396
PMCPMC6250728
OpenAlexW2900581547

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.