ELIZA

return kwic search for significantly out of >500 occurrences
583352 occurrences (No.14 in the rank) during 5 years in the PubMed. [cache]

364) Mice deficient in hepcidin specifically in the colon tumour epithelium, compared with wild-type littermates, exhibit significantly diminished tumour number, burden and size in a sporadic model of CRC, whereas accumulation of intracellular iron by deletion of the iron exporter ferroportin exacerbates these tumour parameters.

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PMID:34155415 DOI:10.1038/s42255-021-00406-7

2021 Nature metabolism

* Hepcidin sequesters iron to sustain nucleotide metabolism and mitochondrial function in colorectal cancer epithelial cells.

- Colorectal cancer (CRC) requires massive iron stores, but the complete mechanisms by which CRC modulates local iron handling are poorly understood. Here, we demonstrate that hepcidin is activated ectopically in CRC. Mice deficient in hepcidin specifically in the colon tumour epithelium, compared with wild-type littermates, exhibit significantly diminished tumour number, burden and size in a sporadic model of CRC, whereas accumulation of intracellular iron by deletion of the iron exporter ferroportin exacerbates these tumour parameters. Metabolomic analysis of three-dimensional patient-derived CRC tumour enteroids indicates a prioritization of iron in CRC for the production of nucleotides, which is recapitulated in our hepcidin/ferroportin mouse CRC models. Mechanistically, our data suggest that iron chelation decreases mitochondrial function, thereby altering nucleotide synthesis, whereas exogenous supplementation of nucleosides or aspartate partially rescues tumour growth in patient-derived enteroids and CRC cell lines in the presence of an iron chelator. Collectively, these data suggest that ectopic hepcidin in the tumour epithelium establishes an axis to sequester iron in order to maintain the nucleotide pool and sustain proliferation in colorectal tumours.

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[frequency of next (right) word to significantly]

(1)44 higher	(17)6 with	(33)4 in	(49)2 faster
(2)35 increased	(18)5 and	(34)4 suppressed	(50)2 increases
(3)33 associated	(19)5 better	(35)3 (p	(51)2 influence
(4)25 reduced	(20)5 enhanced	(36)3 change	(52)2 inhibit
(5)20 lower	(21)5 enriched	(37)3 diminished	(53)2 larger
(6)19 decreased	(22)5 less	(38)3 increase	(54)2 lowered
(7)15 different	(23)5 related	(39)3 longer	(55)2 modified
(8)14 more	(24)4 null	(40)2 (P	(56)2 over
(9)13 greater	(25)4 altered	(41)2 affected	(57)2 positively
(10)12 improved	(26)4 between	(42)2 alleviated	(58)2 prolong
(11)11 correlated	(27)4 by	(43)2 alter	(59)2 reduce
(12)10 inhibited	(28)4 downregulated	(44)2 at	(60)2 reduces
(13)6 attenuated	(29)4 elevated	(45)2 changed	(61)2 reversed
(14)6 predicted	(30)4 impact	(46)2 declined
(15)6 to	(31)4 improve	(47)2 decreased,
(16)6 upregulated	(32)4 improves	(48)2 expanded

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--- WordNet output for significantly --- =>きわめて, 意味深く, 意味ありげに Overview of adv significantly The adv significantly has 3 senses (first 2 from tagged texts) 1. (6) significantly -- (in a statistically significant way; "the two groups differed significantly") 2. (3) significantly -- (in a significant manner; "our budget will be significantly affected by these new cuts") 3. importantly, significantly -- (in an important way or to an important degree; "more importantly, Weber held that the manifold meaning attached to the event by the social scientist could alter his definition of the concrete event itself") --- WordNet end ---