Oncogene, 2015-01, Vol.34 (3), p.323-333
2015
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Estrogen-dependent sushi domain containing 3 regulates cytoskeleton organization and migration in breast cancer cells
- Ist Teil von
- Oncogene, 2015-01, Vol.34 (3), p.323-333
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2015
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Aromatase inhibitors (AIs) are the standard endocrine therapy for postmenopausal breast cancer; however, currently used biomarkers, such as, estrogen receptor-alpha/progesterone receptor (ERα/PR), predict only slightly more than half of the potential responders to AI treatment. To identify novel markers of AI responsiveness, a genome-wide microarray analysis was performed using primary breast tumor samples from 50 postmenopausal women who later developed metastatic breast cancer. Sushi domain containing 3 ( SUSD3 ) is a significantly differentially expressed gene, with 3.38-fold higher mRNA levels in AI-responsive breast tumors vs non-responders ( P <0.001). SUSD3 was highly expressed in ERα-positive breast tumors and treatment with estradiol increased SUSD3 expression in ERα-positive breast cancer cells. Treatment with an antiestrogen or ERα knockdown abolished basal and estradiol-dependent SUSD3 expression. Recruitment of ERα upstream of the transcription start site of SUSD3 was demonstrated by chromatin immunoprecipitation–PCR. Flow cytometric analysis of SUSD3-knockdown cells revealed blunted estradiol effects on progression into S and M phases. SUSD3 was localized to the plasma membrane of breast cancer cells. SUSD3 knockdown decreased the appearance of actin-rich protrusions, stress fibers and large basal focal adhesions, while increasing the presence of cortical actin concomitant with a decrease in Rho and focal adhesion kinase activity. SUSD3-deficient cells demonstrated diminished cell spreading, cell–cell adhesion and motility. In conclusion, SUSD3 is a novel promoter of estrogen-dependent cell proliferation and regulator of cell–cell and cell–substrate interactions and migration in breast cancer. It may serve as a novel predictor of response to endocrine therapy and potential therapeutic target.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0950-9232eISSN: 1476-5594DOI: 10.1038/onc.2013.553Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4096609
- Format
- –
- Schlagworte
- 17β-Estradiol, 631/80/84, 631/80/86, 692/699/67/1347, Actin, Actin Cytoskeleton - metabolism, Antiestrogens, Apoptosis, Aromatase, Aromatase Inhibitors - pharmacology, Blotting, Western, Breast cancer, Breast Neoplasms - genetics, Breast Neoplasms - metabolism, Breast Neoplasms - pathology, Care and treatment, Cell adhesion, Cell adhesion & migration, Cell Biology, Cell Line, Tumor, Cell migration, Cell Movement - genetics, Cell proliferation, Cell spreading, Cellular signal transduction, Chromatin, Cortex, Cytoskeleton, Development and progression, DNA microarrays, Endocrine therapy, Estradiol - analogs & derivatives, Estradiol - pharmacology, Estrogen Receptor alpha - antagonists & inhibitors, Estrogen Receptor alpha - genetics, Estrogen Receptor alpha - metabolism, Estrogen Receptor Antagonists - pharmacology, Estrogens, Estrogens - pharmacology, Female, Flow cytometry, Focal adhesion kinase, Focal Adhesions - genetics, Fulvestrant, Gene expression, Gene Expression Profiling, Gene Expression Regulation, Neoplastic - drug effects, Genetic aspects, Genomes, Health aspects, Human Genetics, Humans, Immunoprecipitation, Internal Medicine, Kinases, MCF-7 Cells, Medicine, Medicine & Public Health, Membrane Proteins - genetics, Membrane Proteins - metabolism, Metastases, Microscopy, Confocal, Oncogenes, Oncology, original-article, Post-menopause, Progesterone, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, Therapeutic applications, Transcription, Tumors