ELIZA

return kwic search for reduced out of >500 occurrences
290904 occurrences (No.84 in the rank) during 5 years in the PubMed. [no cache] 500 found

8) HSF-1 knockdown reduced the ability of Akt to induce Slug expression, indicating an essential role that HSF-1 plays in Akt-induced Slug upregulation.

--- ABSTRACT ---

PMID:24469056 DOI:10.1038/onc.2013.582

2015 Oncogene

* Akt phosphorylates and activates HSF-1 independent of heat shock, leading to Slug overexpression and epithelial-mesenchymal transition (EMT) of HER2-overexpressing breast cancer cells.

- Epithelial-mesenchymal transition (EMT) is an essential step for tumor progression, although the mechanisms driving EMT are still not fully understood. In an effort to investigate these mechanisms, we observed that heregulin (HRG)-mediated activation of HER2, or HER2 overexpression, resulted in EMT, which is accompanied with increased expression of a known EMT regulator Slug, but not TWIST or Snail. We then investigated how HER2 induced Slug expression and found, for the first time, that there are four consensus HSF sequence-binding elements (HSEs), the binding sites for heat shock factor-1 (HSF-1), located in the Slug promoter. HSF-1 bound to and transactivated the Slug promoter independent of heat shock, leading to Slug expression in breast cancer cells. Mutation of the putative HSEs ablated Slug transcriptional activation induced by HRG or HSF-1 overexpression. Knockdown of HSF-1 expression by siRNA reduced Slug expression and HRG-induced EMT. The positive association between HSF-1 and Slug was confirmed by immunohistochemical staining of a cohort of 100 invasive breast carcinoma specimens. While investigating how HER2 activated HSF-1 independent of heat shock, we observed that HER2 activation resulted in concurrent phosphorylation of Akt and HSF-1. We then observed, also for the first time, that Akt directly interacted with HSF-1 and phosphorylated HSF-1 at S326. Inhibition of Akt using siRNA, dominant-negative Akt mutant, or small molecule inhibitors prevented HRG-induced HSF-1 activation and Slug expression. Conversely, constitutively active Akt induced HSF-1 phosphorylation and Slug expression. HSF-1 knockdown reduced the ability of Akt to induce Slug expression, indicating an essential role that HSF-1 plays in Akt-induced Slug upregulation. Altogether, our study uncovered the existence of a novel Akt-HSF-1 signaling axis that leads to Slug upregulation and EMT, and potentially contributes to progression of HER2-positive breast cancer.

--- ABSTRACT END ---

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(1)66 the	(12)4 activity	(24)2 among	(35)2 interhemispheric
(2)30 in	(13)4 both	(25)2 availability	(36)2 it
(3)23 by	(14)4 cell	(26)2 blood	(37)2 likelihood
(4)13 null	(16)3 ability	(27)2 but	(38)2 number
(5)13 to	(17)3 after	(28)2 compared	(39)2 rates
(6)10 glutathione	(18)3 binding	(29)2 effortful	(40)2 stem
(7)8 and	(19)3 or	(30)2 ejection	(41)2 total
(8)8 expression	(20)3 risk	(31)2 following	(42)2 tumor
(9)5 levels	(21)3 sensitivity	(32)2 from	(43)2 which
(10)5 significantly	(22)2 (P	(33)2 glutathione,
(11)4 PGE2	(23)2 BRCA-1	(34)2 hippocampal

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--- WordNet output for reduced --- =>貧しい暮らし, 落ちぶれた生活 Overview of verb reduce The verb reduce has 20 senses (first 11 from tagged texts) 1. (102) reduce, cut down, cut back, trim, trim down, trim back, cut, bring down -- (cut down on; make a reduction in; "reduce your daily fat intake"; "The employer wants to cut back health benefits") 2. (9) reduce -- (make less complex; "reduce a problem to a single question") 3. (5) reduce -- (bring to humbler or weaker state or condition; "He reduced the population to slavery") 4. (3) reduce -- (simplify the form of a mathematical equation of expression by substituting one term for another) 5. (3) reduce -- (lower in grade or rank or force somebody into an undignified situation; "She reduced her niece to a servant") 6. (3) reduce, come down, boil down -- (be the essential element; "The proposal boils down to a compromise") 7. (2) shrink, reduce -- (reduce in size; reduce physically; "Hot water will shrink the sweater"; "Can you shrink this image?") 8. (1) reduce -- (lessen and make more modest; "reduce one's standard of living") 9. (1) reduce, scale down -- (make smaller; "reduce an image") 10. (1) deoxidize, deoxidise, reduce -- (to remove oxygen from a compound, or cause to react with hydrogen or form a hydride, or to undergo an increase in the number of electrons) 11. (1) reduce, tighten -- (narrow or limit; "reduce the influx of foreigners") 12. repress, quash, keep down, subdue, subjugate, reduce -- (put down by force or intimidation; "The government quashes any attempt of an uprising"; "China keeps down her dissidents very efficiently"; "The rich landowners subjugated the peasants working the land") 13. reduce -- (undergo meiosis; "The cells reduce") 14. reduce -- (reposition (a broken bone after surgery) back to its normal site) 15. reduce -- (destress and thus weaken a sound when pronouncing it) 16. abridge, foreshorten, abbreviate, shorten, cut, contract, reduce -- (reduce in scope while retaining essential elements; "The manuscript must be shortened") 17. boil down, reduce, decoct, concentrate -- (be cooked until very little liquid is left; "The sauce should reduce to one cup") 18. reduce, boil down, concentrate -- (cook until very little liquid is left; "The cook reduced the sauce by boiling it for a long time") 19. dilute, thin, thin out, reduce, cut -- (lessen the strength or flavor of a solution or mixture; "cut bourbon") 20. reduce, melt off, lose weight, slim, slenderize, thin, slim down -- (take off weight) Overview of adj reduced The adj reduced has 2 senses (first 2 from tagged texts) 1. (6) decreased, reduced -- (made less in size or amount or degree) 2. (1) reduced, rock-bottom -- (well below normal (especially in price)) --- WordNet end ---