Journal Article

DKFZ-2017-02391

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Navigator-3, a modulator of cell migration, may act as a suppressor of breast cancer progression.

Cohen-Dvashi, H. ; Ben-Chetrit, N. ; Russell, R. ; Carvalho, S. ; Lauriola, M. ; Nisani, S. ; Mancini, M. ; Nataraj, N. ; Kedmi, M. ; Roth, L. ; Köstler, W. ; Zeisel, A. ; Yitzhaky, A. ; Zylberg, J. ; Tarcic, G. ; Eilam, R. ; Wigelman, Y. ; Will, R.DKFZ* ; Lavi, S. ; Porat, Z. ; Wiemann, S.DKFZ* ; Ricardo, S. ; Schmitt, F. ; Caldas, C. ; Yarden, Y.

2015
Wiley-VCH Weinheim

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Please use a persistent id in citations: doi:10.15252/emmm.201404134

Abstract: 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.

Keyword(s): Membrane Proteins ; NAV3 protein, human ; Nerve Tissue Proteins

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Contributing Institute(s):

1. Molekulare Genomanalyse (B050)
2. Microarray Unit (W110)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2015

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Database coverage:
; ; ; BIOSIS Previews ; DOAJ Seal ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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