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S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide.

ABSTRACT: S100A4 (metastasin-1), a metastasis-associated protein and marker of the epithelial to mesenchymal transition, contributes to several hallmarks of cancer and has been implicated in the progression of several types of cancer. However, the impacts of S100A4 signaling in lung cancer progression and its potential use as a target for therapy in lung cancer have not been properly explored. Using established lung cancer cell lines, we demonstrate that S100A4 knockdown reduces cell proliferation, invasion and three-dimensional invasive growth, while overexpression of S100A4 increases invasive potential. In patient-derived tissues, S100A4 is preferentially elevated in lung adenocarcinoma. This elevation is associated with lymphovascular invasion and decreased overall survival. In addition, depletion of S100A4 by shRNA inhibits NF-?B activity and decreases TNF?-induced MMP9 expression. Furthermore, inhibition of the NF-?B/MMP9 axis decreases lung carcinoma invasive potential. Niclosamide, a reported inhibitor of S100A4, blocks expression and function of S100A4 with a reduction in proliferation, invasion and NF-?B-mediated MMP9 expression. Collectively, this study highlights the importance of the S100A4/NF-?B/MMP9 axis in lung cancer invasion and provides a rationale for targeting S100A4 to combat lung cancer.

SUBMITTER: Stewart RL

PROVIDER: S-EPMC5085181 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide.

Stewart Rachel L RL Carpenter Brittany L BL West Dava S DS Knifley Teresa T Liu Lili L Wang Chi C Weiss Heidi L HL Gal Tamas S TS Durbin Eric B EB Arnold Susanne M SM O'Connor Kathleen L KL Chen Min M

Oncotarget 20160601 23

S100A4 (metastasin-1), a metastasis-associated protein and marker of the epithelial to mesenchymal transition, contributes to several hallmarks of cancer and has been implicated in the progression of several types of cancer. However, the impacts of S100A4 signaling in lung cancer progression and its potential use as a target for therapy in lung cancer have not been properly explored. Using established lung cancer cell lines, we demonstrate that S100A4 knockdown reduces cell proliferation, invasi ...[more]

PMID: 27127879

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Project description:BackgroundMedication guides are required documents to be distributed to patients in order to convey serious risks associated with certain prescribed medicines. Little is known about the effectiveness of this information to adequately inform patients on safe use.ObjectiveTo examine the readability, suitability, and comprehensibility of medication guides, particularly for those with limited literacy.DesignAssessments of suitability and readability of 185 medication guides, and a sub-study examining change in suitability and readability from 2006 to 2010 among 32 of the medication guides (Study 1); 'open book' comprehension assessment of medication guides (Study 2).SettingTwo general internal medicine clinics in Chicago, IL.PatientsFour hundred and forty-nine adults seeking primary care services, ages 18-85.MeasurementsFor Study 1, the Suitability Assessment of Materials (SAM) and Lexile score for readability. For Study 2, a tailored comprehension assessment of content found in three representative medication guides.ResultsThe 185 analyzed medication guides were on average 1923 words (SD = 1022), with a mean reading level of 10-11th grade. Only one medication guide was deemed suitable in SAM analyses. None provided summaries or reviews, or framed the context first, while very few were rated as having made the purpose evident (8 %), or limited the scope of content (22 %). For Study 2, participants' comprehension of medication guides was poor (M = 52.7 % correct responses, SD = 22.6). In multivariable analysis, low and marginal literacy were independently associated with poorer understanding (β = -14.3, 95 % CI -18.0 - -10.6, p < 0.001; low: β = -23.7, 95 % CI -28.3 - -19.0, p < 0.001).ConclusionCurrent medication guides are of little value to patients, as they are too complex and difficult to understand especially for individuals with limited literacy. Explicit guidance is offered for improving these print materials.

Dataset Information

S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide.

Publications

S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide.

Similar Datasets

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