Navigator‐3, a modulator of cell migration, may act as a suppressor of breast cancer progression

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.

MiR-21 promoted proliferation and migration in hepatocellular carcinoma through negative regulation of Navigator-3

“…With regard to the NAV-3 in HCC, there has been paucity of data till now. In our study, our results showed that knock-down of NAV-3 can promote both the proliferation and migration of HCC cells, which was in agreement with findings by Cohen-Dvashi H and colleagues [11] in breast cancer. In HCC tissues, we found that lower expression of NAV-3 was significantly associated with poor prognosis, which was also consistent with conclusions given by Carlsson E et al [15] in nervous system tumors and Cohen-Dvashi H et al [11] in breast cancer that NAV-3 may be a potential new prognostic biomarker, despite the limited cases of HCC we've employed and enrolled.…”

“…No more study mentioned any miRNA that could potentially regulate NAV-3 in diseases in any form. Consequently, based on the previous studies in cancers [10,11,15], it fairly can be suggested that NAV-3 may play an anti-oncogenic role in cancers, which was backed up by our current study in HCC.…”

“…In breast cancer, Cohen-Dvashi H et al proposed that NAV-3 inhibited breast cancer progression by regulating microtubule dynamics, playing a metastasis-suppressing role [11]. With regard to the NAV-3 in HCC, there has been paucity of data till now.…”

“…Silencing of NAV-3 leads to the variation of genes that mostly related to inflammation [9,10], suggesting that NAV-3 has a role in linking inflammation to cancer development. In addition, Cohen-Dvashi H et al discovered that silencing of NAV-3 increased metastasis in breast cancer animal model, indicating that NAV-3 might play an metastasis-suppressing role in breast cancer [11]. No study regarding NAV-3 in HCC has been available till now.…”

Establishment of a novel human medulloblastoma cell line characterized by highly aggressive stem-like cells

“…The loss of chromosome 12q21.2 encompasses NAV3, whose silencing was recently reported to inhibit apoptosis of breast cancer cells (Cohen-Dvashi et al 2015). USP-13-Med cells also seem to have dysfunctional p53 signaling.…”