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505522 occurrences (No.25 in the rank) during 5 years in the PubMed. [no cache] 500 found

302) SIRT1 regulates Dishevelled (DVL) protein levels in cancer cells, and DVL along with TIAM1 are known to augment Rac activation; however, SIRT1 or 2 has not been previously linked with TIAM1.

--- ABSTRACT ---

PMID:24362520 DOI:10.1038/onc.2013.549

2015 Oncogene

* The sirtuins promote Dishevelled-1 scaffolding of TIAM1, Rac activation and cell migration.

- Rac1-GTPases serve as intermediary cellular switches, which conduct transient and constitutive signals from upstream cues, including those from Ras oncoproteins. Although the sirtuin1 (SIRT1) deacetylase is overexpressed in several human cancers and has recently been linked to cancer cell motility as a context-dependent regulator of multiple pathways, its role in Rac1 activation has not been reported. Similarly, SIRT2 has been demonstrated to be upregulated in some cancers; however, studies have also reported its role in tumor suppression. Here, we demonstrate that SIRT1 and SIRT2 positively regulate the levels of Rac1-GTP and the activity of T-cell lymphoma invasion and metastasis 1 (TIAM1), a Rac guanine nucleotide exchange factor (GEF). Transient inhibition of SIRT1 and SIRT2 resulted in increased acetylation of TIAM1, whereas chronic SIRT2 knockdown resulted in enhanced acetylation of TIAM1. SIRT1 regulates Dishevelled (DVL) protein levels in cancer cells, and DVL along with TIAM1 are known to augment Rac activation; however, SIRT1 or 2 has not been previously linked with TIAM1. We found that diminished sirtuin activity led to the disruption of the DVL1-TIAM1 interaction. We hence propose a model for Rac activation where SIRT1/2 positively modulates the DVL/TIAM1/Rac axis and promotes sustained pathway activation.

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(1)65 null	(14)6 therapy	(27)3 of	(40)2 epigenetics
(2)48 cells	(15)6 tissues	(28)3 patients,	(41)2 growth
(3)33 and	(16)5 cells,	(29)3 research	(42)2 initiation
(4)32 cell	(17)5 progression	(30)3 was	(43)2 prevention
(5)23 patients	(18)5 registries	(31)2 (GC)	(44)2 registry
(6)15 in	(19)4 at	(32)2 biology	(45)2 study
(7)14 is	(20)4 deaths	(33)2 but	(46)2 susceptibility
(8)12 risk	(21)4 has	(34)2 can	(47)2 than
(9)12 screening	(22)4 mortality	(35)2 care	(48)2 treated
(10)12 stem	(23)3 (CRC)	(36)2 development	(49)2 treatment
(11)9 survivors	(24)3 as	(37)2 diagnostic	(50)2 using
(12)7 with	(25)3 cases	(38)2 drug
(13)6 are	(26)3 metabolism	(39)2 drugs

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--- WordNet output for cancer --- =>【病名】がん, 悪性腫瘍(しゅよう), がん腫, 社会悪, 癌 Overview of noun cancer The noun cancer has 5 senses (first 1 from tagged texts) 1. (15) cancer, malignant neoplastic disease -- (any malignant growth or tumor caused by abnormal and uncontrolled cell division; it may spread to other parts of the body through the lymphatic system or the blood stream) 2. Cancer, Crab -- ((astrology) a person who is born while the sun is in Cancer) 3. Cancer -- (a small zodiacal constellation in the northern hemisphere; between Leo and Gemini) 4. Cancer, Cancer the Crab, Crab -- (the fourth sign of the zodiac; the sun is in this sign from about June 21 to July 22) 5. Cancer, genus Cancer -- (type genus of the family Cancridae) --- WordNet end ---