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000126276 037__ $$aDKFZ-2017-02391
000126276 041__ $$aeng
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000126276 1001_ $$aCohen-Dvashi, Hadas$$b0
000126276 245__ $$aNavigator-3, a modulator of cell migration, may act as a suppressor of breast cancer progression.
000126276 260__ $$aWeinheim$$bWiley-VCH$$c2015
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000126276 520__ $$aDissemination of primary tumor cells depends on migratory and invasive attributes. Here, we identify Navigator-3 (NAV3), a gene frequently mutated or deleted in human tumors, as a regulator of epithelial migration and invasion. Following induction by growth factors, NAV3 localizes to the plus ends of microtubules and enhances their polarized growth. Accordingly, NAV3 depletion trimmed microtubule growth, prolonged growth factor signaling, prevented apoptosis and enhanced random cell migration. Mathematical modeling suggested that NAV3-depleted cells acquire an advantage in terms of the way they explore their environment. In animal models, silencing NAV3 increased metastasis, whereas ectopic expression of the wild-type form, unlike expression of two, relatively unstable oncogenic mutants from human tumors, inhibited metastasis. Congruently, analyses of > 2,500 breast and lung cancer patients associated low NAV3 with shorter survival. We propose that NAV3 inhibits breast cancer progression by regulating microtubule dynamics, biasing directionally persistent rather than random migration, and inhibiting locomotion of initiated cells.
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000126276 650_7 $$2NLM Chemicals$$aMembrane Proteins
000126276 650_7 $$2NLM Chemicals$$aNAV3 protein, human
000126276 650_7 $$2NLM Chemicals$$aNerve Tissue Proteins
000126276 7001_ $$aBen-Chetrit, Nir$$b1
000126276 7001_ $$aRussell, Roslin$$b2
000126276 7001_ $$aCarvalho, Silvia$$b3
000126276 7001_ $$aLauriola, Mattia$$b4
000126276 7001_ $$aNisani, Sophia$$b5
000126276 7001_ $$aMancini, Maicol$$b6
000126276 7001_ $$aNataraj, Nishanth$$b7
000126276 7001_ $$aKedmi, Merav$$b8
000126276 7001_ $$aRoth, Lee$$b9
000126276 7001_ $$aKöstler, Wolfgang$$b10
000126276 7001_ $$aZeisel, Amit$$b11
000126276 7001_ $$aYitzhaky, Assif$$b12
000126276 7001_ $$aZylberg, Jacques$$b13
000126276 7001_ $$aTarcic, Gabi$$b14
000126276 7001_ $$aEilam, Raya$$b15
000126276 7001_ $$aWigelman, Yoav$$b16
000126276 7001_ $$0P:(DE-He78)18218139eec55d83cf82679934e5cd75$$aWill, Rainer$$b17$$udkfz
000126276 7001_ $$aLavi, Sara$$b18
000126276 7001_ $$aPorat, Ziv$$b19
000126276 7001_ $$0P:(DE-He78)f6bebe05e7a748d3cbf9f59659567d52$$aWiemann, Stefan$$b20$$udkfz
000126276 7001_ $$aRicardo, Sara$$b21
000126276 7001_ $$aSchmitt, Fernando$$b22
000126276 7001_ $$aCaldas, Carlos$$b23
000126276 7001_ $$aYarden, Yosef$$b24
000126276 773__ $$0PERI:(DE-600)2485479-7$$a10.15252/emmm.201404134$$gVol. 7, no. 3, p. 299 - 314$$n3$$p299 - 314$$tEMBO molecular medicine$$v7$$x1757-4684$$y2015
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