Jab1 is overexpressed in human breast cancer and is a downstream target for HER-2/neu

Hsu, Ming-Chuan; Chai, Chee‐Yin; Hou, Ming‐Feng; Chang, Hsuan; Chen, Wan‐Tzu; Hung, Wen‐Chun

doi:10.1038/modpathol.2008.23

Cited by 26 publications

(27 citation statements)

References 28 publications

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“…In vitro invasion assay was performed as described previously [19], [23] by using 24-well transwell units with poly-carbonate filters (pore size 8 µm) coated on the upper side with Matrigel (BD Biosciences). 5×10 3 cells in 100 µl of medium were treated with 0.1% DMSO (vehicle) or 10 µM of AL10 for 24 h. Cells were harvested and placed onto the upper part of the Transwell unit.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Chemokine (C-C Motif) Receptor 7 Sialylation Suppresses CCL19-Stimulated Proliferation, Invasion and Anti-Anoikis

Chang

Chiang

et al. 2014

PLoS ONE

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Chemokine (C-C motif) receptor 7 (CCR7) is involved in lymph-node homing of naive and regulatory T cells and lymphatic metastasis of cancer cells. Sialic acids comprise a group of monosaccharide units that are added to the terminal position of the oligosaccharide chain of glycoproteins by sialyation. Recent studies suggest that aberrant sialylation of receptor proteins contributes to proliferation, motility, and drug resistance of cancer cells. In this study, we addressed whether CCR7 is a sialylated receptor protein and tried to elucidate the effect of sialylation in the regulation of signal transduction and biological function of CCR7. Our results demonstrated that α-2, 3-sialyltransferase which catalyze sialylation reaction in vivo was overexpressed in breast tumor tissues and cell lines. Lectin blot analysis clearly demonstrated that CCR7 receptor was sialyated in breast cancer cells. Chemokine (C-C motif) ligand 19 (CCL19), the cognate ligand for CCR7, induced the activation of extracellular signal-regulated kinase (ERK) and AKT signaling and increased the expression of cell cycle regulatory proteins and proliferation of breast cancer cells. When cells were pre-treated with a sialyltransferase inhibitor AL10 or sialidase, CCL19-induced cell growth was significantly suppressed. CCL19 also increased invasion and prevented anoikis by up-regulating pro-survival proteins Bcl-2 and Bcl-xL. Inhibition of sialylation by AL10 totally abolished these effects. Finally, we showed that AL10 inhibited tumorigenicity of breast cancer in experimental animals. Taken together, we demonstrate for the first time that CCR7 receptor is a sialylated protein and sialylation is important for the paracrine stimulation by its endogenous ligand CCL19. In addition, inhibition of aberrant sialylation of CCR7 suppresses proliferation and invasion and triggers anoikis in breast cancer cells. Targeting of sialylation enzymes may be a novel strategy for breast cancer treatment.

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Section: Methodsmentioning

confidence: 99%

Inhibition of Chemokine (C-C Motif) Receptor 7 Sialylation Suppresses CCL19-Stimulated Proliferation, Invasion and Anti-Anoikis

Chang

Chiang

et al. 2014

PLoS ONE

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Section: Introductionmentioning

confidence: 99%

“…Studies have demonstrated Jab1/CSN5 overexpression in breast cancer [92,98,99]. The breast cancer driving EGFR receptors including the oncogenic HER2/neu have been correlated with increased Jab1/CSN5 expression in clinical samples [98,99]. Jab1/CSN5 was shown to be a target of EGFR signaling in estrogen receptor-alpha-negative (ERα - ) breast cancer and the translocation of Jab1/CSN5 to the nucleus was shown to be mediated through the ERK signaling pathway [98].…”

Section: Introductionmentioning

confidence: 99%

“…Jab1/CSN5 was shown to be a target of EGFR signaling in estrogen receptor-alpha-negative (ERα - ) breast cancer and the translocation of Jab1/CSN5 to the nucleus was shown to be mediated through the ERK signaling pathway [98]. Similarly, HER-2/neu was found to activate Jab1/CSN5 expression through the AKT/bet-catenin pathway [99]. The involvement of Jab1/CSN5 in breast tumorigenesis appears to be linked to the expression of EGFR and HER-2/neu receptors and may in part mediate downstream signaling events that contribute to the progression of tumor growth.…”

Section: Introductionmentioning

confidence: 99%

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JAB1/CSN5: a new player in cell cycle control and cancer

2010

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c-Jun activation domain-binding protein-1 (Jab1) acts as a modulator of intracellular signaling and affects cellular proliferation and apoptosis, through its existence as a monomer or as the fifth component of the constitutive photomorphogenic-9 signalosome (CSN5). Jab1/CSN5 is involved in transcription factor specificity, deneddylation of NEDD8, and nuclear-to-cytoplasmic shuttling of key molecules. Jab1/CSN5 activities positively and negatively affect a number of pathways, including integrin signaling, cell cycle control, and apoptosis. Also, more recent studies have demonstrated the intriguing roles of Jab1/CSN5 in regulating genomic instability and DNA repair. The effects of Jab1/CSN5's multiple protein interactions are generally oncogenic in nature, and overexpression of Jab1/CSN5 in cancer provides evidence that it is involved in the tumorigenic process. In this review, we highlight our current knowledge of Jab1/CSN5 function and the recent discoveries in dissecting the Jab1 signaling pathway. Further, we also discuss the regulation of Jab1/CSN5 in cancers and its potential as a therapeutic target.

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“…Kip1 protein to enhance ubiquitin-mediated degradation by increasing affinity with JAB1 through the HER2/Grb2/Ras/MAPK pathway (29,30), promoting p27…”

Section: Discussionmentioning

confidence: 99%

Trastuzumab enhances the anti-tumor effects of the histone deacetylase inhibitor sodium butyrate on a HER2-overexpressing breast cancer cell line

Chen

Feng²,

Xu³

et al. 2011

Int J Mol Med

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Abstract. Trastuzumab has efficacy to improve the effect of cytotoxic drugs, such as paclitaxel and anthracyclin, against HER2-overexpressing breast cancer cells. Sodium butyrate (NaB), a histone deacetylase inhibitor, is known to have antitumoral properties. However, whether and how trastuzumab possesses the potential to synergize the anti-tumor effect of NaB on breast cancer cells is still equivocal. To elucidate whether combined treatment with NaB and trastuzumab exerts antitumor effects on a HER2-overexpressing breast cancer cell line, SKBR3 cells were treated with NaB alone or in combination with trastuzumab, and the effects on proliferation and cell cycle progression were analyzed. Combinatory treatment with NaB (4 mmol/l) and trastuzumab (20 µg/ml) significantly increased the growth-inhibitory effect on SKBR3 breast cancer cells, in comparison to NaB or trastuzumab treatment alone. The growthinhibitory effect of the combination of NaB and trastuzumab was accompanied by elevated mRNA and protein levels of the cyclin-dependent kinase inhibitor p27 Kip1 . In contrast, this effect was absent in HER2-negative HCC1937 cells. In conclusion, trastuzumab significantly improved the antitumor effect of NaB on HER2-overexpressing breast cancer cell line in vitro.

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Jab1 is overexpressed in human breast cancer and is a downstream target for HER-2/neu

Cited by 26 publications

References 28 publications

Inhibition of Chemokine (C-C Motif) Receptor 7 Sialylation Suppresses CCL19-Stimulated Proliferation, Invasion and Anti-Anoikis

Inhibition of Chemokine (C-C Motif) Receptor 7 Sialylation Suppresses CCL19-Stimulated Proliferation, Invasion and Anti-Anoikis

JAB1/CSN5: a new player in cell cycle control and cancer

Trastuzumab enhances the anti-tumor effects of the histone deacetylase inhibitor sodium butyrate on a HER2-overexpressing breast cancer cell line

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