Focal adhesion kinase (FAK) activation by estrogens involves GPER in triple-negative breast cancer cells.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30728047", "kind": "science-record", "revision": 8, "content_hash": "sha256:d6e3a438877488ad4ea73b677dd757fa30b7166d5f44dc63c57e8913c9b82856", "created_at": "2026-11-01T15:40:42Z", "updated_at": "2026-11-01T22:43:47Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Focal adhesion kinase (FAK) activation by estrogens involves GPER in triple-negative breast cancer cells.", "doi": "10.1186/s13046-019-1056-8", "pmid": "30728047", "authors": ["Damiano Cosimo Rigiracciolo", "Maria Francesca Santolla", "Rosamaria Lappano", "Adele Vivacqua", "Francesca Cirillo", "Giulia Raffaella Galli", "Marianna Talia", "Lucia Muglia", "Michele Pellegrino", "Nijiro Nohata", "Maria Teresa Di Martino", "Marcello Maggiolini"], "journal": "Journal of experimental & clinical cancer research : CR", "year": 2019, "abstract": "BACKGROUND: Focal adhesion kinase (FAK) is a cytoplasmatic protein tyrosine kinase that associates with both integrins and growth factor receptors toward the adhesion, migration and invasion of cancer cells. The G-protein coupled estrogen receptor (GPER) has been involved in the stimulatory action of estrogens in breast tumor. In this study, we have investigated the engagement of FAK by GPER signaling in triple negative breast cancer (TNBC) cells.\nMETHODS: Publicly available large-scale database and patient data sets derived from \"The Cancer Genome Atlas\" (TCGA; www.cbioportal.org ) were used to assess FAK expression in TNBC, non-TNBC tumors and normal breast tissues. MDA-MB 231 and SUM159 TNBC cells were used as model system. The levels of phosphorylated FAK, other transduction mediators and target genes were detected by western blotting analysis. Focal adhesion assay was carried out in order to determine the focal adhesion points and the formation of focal adhesions (FAs). Luciferase assays were performed to evaluate the promoters activity of c-FOS, EGR1 and CTGF upon GPER activation. The mRNA expression of the aforementioned genes was measured by real time-PCR. Boyden chamber and wound healing assays were used in order to evaluate cell migration. The statistical analysis was performed by ANOVA.\nRESULTS: We first determined by bioinformatic analysis that the mRNA expression levels of the gene encoding FAK, namely PTK2, is higher in TNBC respect to non-TNBC and normal breast tissues. Next, we found that estrogenic GPER signaling triggers Y397 FAK phosphorylation as well as the increase of focal adhesion points (FAs) in TNBC cells. Besides, we ascertained that GPER and FAK activation are involved in the STAT3 nuclear accumulation and gene expression changes. As biological counterpart, we show that FAK inhibition prevents the migration of TNBC cells upon GPER activation.\nCONCLUSIONS: The present data provide novel insights regarding the action of FAK in TNBC. Moreover, on the basis of our findings estrogenic GPER signaling may be considered among the transduction mechanisms engaging FAK toward breast cancer progression.", "claims": [{"id": "claim-method", "statement": "The statistical analysis was performed using ANOVA followed by Newman–Keuls’ testing to determine differences in means.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30728047", "locator": "sections[13] \"Statistical analysis\" paragraph 2", "quote": "The statistical analysis was performed using ANOVA followed by Newman–Keuls’ testing to determine differences in means."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Availability of data and materialsNot applicable.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30728047", "locator": "sections[24] \"ack\" paragraph 1", "quote": "Availability of data and materialsNot applicable."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30728047"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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