* Estrogen-dependent sushi domain containing 3 regulates cytoskeleton organization and migration in breast cancer cells.
- 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.
Overview of verb demonstrate
The verb demonstrate has 4 senses (first 4 from tagged texts)
1. (24) show, demo, exhibit, present, demonstrate -- (give an exhibition of to an interested
audience; "She shows her dogs frequently"; "We will demo the new software in Washington")
2. (22) prove, demonstrate, establish, show, shew -- (establish the validity of something, as by an
example, explanation or experiment; "The experiment demonstrated the instability of the compound";
"The mathematician showed the validity of the conjecture")
3. (2) attest, certify, manifest, demonstrate, evidence -- (provide evidence for; stand as proof of;
show by one's behavior, attitude, or external attributes; "His high fever attested to his illness";
"The buildings in Rome manifest a high level of architectural sophistication"; "This decision
demonstrates his sense of fairness")
4. (1) demonstrate, march -- (march in protest; take part in a demonstration; "Thousands
demonstrated against globalization during the meeting of the most powerful economic nations in
Seattle")
Overview of adj demonstrated
The adj demonstrated has 1 sense (first 1 from tagged texts)
1. (1) demonstrated -- (having been demonstrated or verified beyond doubt)
--- WordNet end ---