Notch signaling as a therapeutic target for breast cancer treatment?

Han, Jianxun; Hendzel, Michael J.; Allalunis‐Turner, Joan

doi:10.1186/bcr2875

Cited by 51 publications

(46 citation statements)

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“…Meanwhile, Yuan et al [32] indicated that higher expression of Notch signaling was associated with a greater possibility of lymph node metastasis (LNM) and higher TNM stages. Notably, previous studies have suggested that the activation of Notch promoted the expansion of BCSCs and was associated with the development and progression of breast cancer [33,34]. Breast cancer cells have also been hypothesized to acquire stem cell-like properties associated with EMT [35], for which snail1 activity is required [36].…”

Section: Sensitivity Analysismentioning

confidence: 99%

SATB1 is Correlated with Progression and Metastasis of Breast Cancers: A Meta-Analysis

Pan

Wei

et al. 2016

Cell Physiol Biochem

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Background/Aims: Several researches have evaluated the significance of SATB1 (Special AT-rich sequence binding protein 1) expression in breast cancers (BCs), but the results have been disputed, especially in the aspects of clinicopathological features and prognosis. Therefore, our study aimed to use a meta-analysis to summarize the clinical and prognostic relevance of SATB1 gene expression in BCs. Methods: A literature search of PubMed, EMBASE, Cochrane library, Chinese Wanfang and CNKI was performed to identify eligible studies. Ten studies total, comprising 5,185 patients (1,699 SATB1-positive and 3,486 SATB1-negative), were enrolled in our study, which was performed using Revman5.3 Software and Stata11.0 Software. Results: This meta-analysis showed that the expression of SATB1 was significantly higher in breast cancer than in normal tissues (OR = 12.28; 95%CI = 6.01-25.09), and was statistically related to several clinicopathological parameters, including lymph node metastasis (OR = 1.55, 95%CI = 1.01-2.39) and Tumor Node Metastasis(TNM) stage (OR = 0.35, 95%CI = 0.22-0.56). However, the level of SATB1 was not statistically associated with the age (OR = 1.13, 95%CI = 0.87-1.46), tumour size (OR = 0.72, 95%CI = 0.44-1.19), estrogen receptor (OR = 0.78, 95%CI = 0.55-1.09), progesterone receptor (OR = 0.64, 95%CI = 0.32-1.29), HER2 status (OR=1.98, 95%CI = 0.74-5.30), and histological type (OR = 0.49, 95%CI = 0.22-1.11). Conclusion: High expression of SATB1 was significantly correlated with tumourigenesis and metastasis of BCs, indicating poor prognosis for patients. SATB1 could serve as a potential marker for detection and prognosis evaluation of breast cancers.

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Section: Sensitivity Analysismentioning

confidence: 99%

SATB1 is Correlated with Progression and Metastasis of Breast Cancers: A Meta-Analysis

Pan

Wei

et al. 2016

Cell Physiol Biochem

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“…In addition to critical roles in development, Notch signaling has been implicated in cancers such as breast, lung and pancreatic cancers and leukemia, where activation of Notch pathways can promote proliferation, prevent differentiation, and promote metastasis21222324. Disruption of the Notch signaling pathways can affect cell growth, cell fate, angiogenesis and apoptosis.…”

mentioning

confidence: 99%

Macrophage-dependent tumor cell transendothelial migration is mediated by Notch1/MenaINV-initiated invadopodium formation

Pignatelli

Bravo‐Cordero

Roh-Johnson

et al. 2016

Sci Rep

114

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The process of intravasation involving transendothelial migration is a key step in metastatic spread. How the triple cell complex composed of a macrophage, Mena over-expressing tumor cell and endothelial cell, called the tumor microenvironment of metastasis (TMEM), facilitates tumor cell transendothelial migration is not completely understood. Previous work has shown that the physical contact between a macrophage and tumor cell results in the formation of invadopodia, actin-rich matrix degrading protrusions, important for tumor cell invasion and transendothelial migration and tumor cell dissemination. Herein, we show that the macrophage-induced invadopodium is formed through a Notch1/MenaINV signaling pathway in the tumor cell upon macrophage contact. This heterotypic tumor cell – macrophage interaction results in the upregulation of MenaINV through the activation of MENA transcription. Notch1 and MenaINV expression are required for tumor cell transendothelial migration, a necessary step during intravasation. Inhibition of the Notch signaling pathway blocked macrophage-induced invadopodium formation in vitro and the dissemination of tumor cells from the primary tumor in vivo. Our findings indicate a novel role for Notch1 signaling in the regulation of MenaINV expression and transendothelial migration and provide mechanistic information essential to the use of therapeutic inhibitors of metastasis.

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“…The development of NOTCH4-targeted inhibition therapies has received much attention, particularly in cancer treatment (36). Our results indicate that patients with bipolar disorder show enhanced NOTCH4 activation, which provides us with new study opportunities for treatment options in this patient group.…”

Section: Discussionmentioning

confidence: 75%