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return kwic search for novel out of >500 occurrences
330250 occurrences (No.59 in the rank) during 5 years in the PubMed. [no cache] 500 found

116) Here, we show that Hedgehog acyltransferase (Hhat), the enzyme responsible for the attachment of palmitate onto Shh, is a novel target for inhibition of Shh signaling in pancreatic cancer cells.

--- ABSTRACT ---

PMID:24469057 DOI:10.1038/onc.2013.575

2015 Oncogene

* Hedgehog acyltransferase as a target in pancreatic ductal adenocarcinoma.

- Sonic Hedgehog (Shh) is abnormally expressed in pancreatic cancer and is associated with disease onset and progression. Inhibition of Shh signaling is thus an attractive clinical target for therapeutic intervention. Most efforts to block Shh signaling have focused on inhibitors of Smoothened, which target the canonical Shh signaling pathway. These approaches have met with limited success, in part due to development of resistance-conferring mutations and contributions from non-canonical signaling pathways. Here, we show that Hedgehog acyltransferase (Hhat), the enzyme responsible for the attachment of palmitate onto Shh, is a novel target for inhibition of Shh signaling in pancreatic cancer cells. Depletion of Hhat with lentivirally delivered small hairpin RNA decreased both anchorage-dependent and independent proliferation of human pancreatic cancer cells. In vivo, Hhat knockdown led to reduction of tumor growth in a mouse xenograft model of pancreatic cancer. RU-SKI 43, a small molecule inhibitor of Hhat recently developed by our group, reduced pancreatic cancer cell proliferation and Gli-1 activation through Smoothened-independent non-canonical signaling. In addition, RU-SKI 43 treatment inhibited two key proliferative pathways regulated by Akt and mTOR. This work demonstrates that Hhat has a critical role in pancreatic cancer and that a small molecule inhibitor of Hhat can successfully block pancreatic cancer cell proliferation. It also highlights the importance of developing optimized Hhat inhibitors to be used as therapeutics in pancreatic cancer, as well as in other malignancies characterized by Shh overexpression.

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(1)22 therapeutic	(17)3 mutation	(33)2 approaches	(49)2 information
(2)11 and	(18)3 paradigm	(34)2 autosomal	(50)2 inhibitors
(3)8 mechanism	(19)3 role	(35)2 candidate	(51)2 learning
(4)8 method	(20)3 strain	(36)2 cardiac	(52)2 modulators
(5)7 approach	(21)3 target	(37)2 clinical	(53)2 object
(6)7 mutations	(22)3 targeted	(38)2 compounds	(54)2 oral
(7)6 therapies	(23)3 targets	(39)2 data	(55)2 polymer
(8)5 technique	(24)3 treatment	(40)2 described	(56)2 potent
(9)4 strategies	(25)3 type	(41)2 dual	(57)2 prognostic
(10)4 strategy	(26)3 words	(42)2 electroporation	(58)2 putative
(11)4 surgical	(27)2 null	(43)2 finding	(59)2 recombinants
(12)3 antibacterial	(28)2 anti-tumor	(44)2 findings	(60)2 results
(13)3 drug	(29)2 antibiotic	(45)2 form	(61)2 therapeutical
(14)3 homozygous	(30)2 anticancer	(46)2 genetic	(62)2 titanium
(15)3 insights	(31)2 application	(47)2 imaging	(63)2 treatments
(16)3 mechanisms	(32)2 applications	(48)2 in

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--- WordNet output for novel --- =>1.よく知られていない, 新しい, 珍奇な, 異常な, 新奇な, 目新しい, 2.(長編)小説 Overview of noun novel The noun novel has 2 senses (first 1 from tagged texts) 1. (17) novel -- (an extended fictional work in prose; usually in the form of a story) 2. novel -- (a printed and bound book that is an extended work of fiction; "his bookcases were filled with nothing but novels"; "he burned all the novels") Overview of adj novel The adj novel has 2 senses (first 1 from tagged texts) 1. (6) fresh, new, novel -- (original and of a kind not seen before; "the computer produced a completely novel proof of a well-known theorem") 2. novel, refreshing -- (pleasantly new or different; "common sense of a most refreshing sort") --- WordNet end ---