TY  - JOUR
AU  - Cohen-Dvashi, Hadas
AU  - Ben-Chetrit, Nir
AU  - Russell, Roslin
AU  - Carvalho, Silvia
AU  - Lauriola, Mattia
AU  - Nisani, Sophia
AU  - Mancini, Maicol
AU  - Nataraj, Nishanth
AU  - Kedmi, Merav
AU  - Roth, Lee
AU  - Köstler, Wolfgang
AU  - Zeisel, Amit
AU  - Yitzhaky, Assif
AU  - Zylberg, Jacques
AU  - Tarcic, Gabi
AU  - Eilam, Raya
AU  - Wigelman, Yoav
AU  - Will, Rainer
AU  - Lavi, Sara
AU  - Porat, Ziv
AU  - Wiemann, Stefan
AU  - Ricardo, Sara
AU  - Schmitt, Fernando
AU  - Caldas, Carlos
AU  - Yarden, Yosef
TI  - Navigator-3, a modulator of cell migration, may act as a suppressor of breast cancer progression.
JO  - EMBO molecular medicine
VL  - 7
IS  - 3
SN  - 1757-4684
CY  - Weinheim
PB  - Wiley-VCH
M1  - DKFZ-2017-02391
SP  - 299 - 314
PY  - 2015
AB  - Dissemination 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.
KW  - Membrane Proteins (NLM Chemicals)
KW  - NAV3 protein, human (NLM Chemicals)
KW  - Nerve Tissue Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:25678558
C2  - pmc:PMC4364947
DO  - DOI:10.15252/emmm.201404134
UR  - https://inrepo02.dkfz.de/record/126276
ER  -