scholarly journals Reactivation of BMP signaling by suboptimal concentrations of MEK inhibitor and FK506 reduces organ-specific breast cancer metastasis

2020 ◽  
Vol 493 ◽  
pp. 41-54
Author(s):  
Jiang Ren ◽  
Yanhong Wang ◽  
Thomas Ware ◽  
Josephine Iaria ◽  
Peter ten Dijke ◽  
...  
2012 ◽  
Vol 17 (2) ◽  
pp. 135-145 ◽  
Author(s):  
Sébastien Nola ◽  
Soraya Sin ◽  
Florian Bonin ◽  
Rosette Lidereau ◽  
Keltouma Driouch

2021 ◽  
Vol 32 ◽  
pp. S493-S494
Author(s):  
A. Chramiec ◽  
E. Öztürk ◽  
M. Wang ◽  
K. Ronaldson-Bouchard ◽  
D.N. Tavakol ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2095
Author(s):  
Min Soo Kim ◽  
Wook Jin

We have previously observed that tropomyosin receptor kinase B (TrkB) induces breast cancer metastasis by activating both the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) and phosphatidylinositol-3-Kinase (PI3K)/AKT signaling pathways and inhibiting runt-related transcription factor 3 (RUNX3) and kelch-like ECH-associated protein 1 (KEAP1). These studies indicated that TrkB expression is crucial to the pathogenesis of breast cancer. However, how TrkB regulates bone morphogenetic protein (BMP) signaling and tumor suppression is largely unknown. Herein, we report that TrkB is a key regulator of BMP-mediated tumor suppression. TrkB enhances the metastatic potential of cancer cells by promoting cell anchorage-independent growth, migration, and suppressing BMP-2-mediated growth inhibition. TrkB inhibits the BMP-mediated activation of SMAD family member 1 (SMAD1) by promoting the formation of the TrkB/BMP type II receptor complex and suppresses RUNX3 by depleting BMP receptor I (BMPRI) expression. In addition, the knockdown of TrkB restored the tumor-inhibitory effect of BMP-2 via the activation of SMAD1. Moreover, the TrkB kinase activity was required for its effect on BMP signaling. Our study identified a unique role of TrkB in the regulation of BMP-mediated growth inhibition and BMP-2-induced RUNX3 expression.


2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yufang Tan ◽  
Xiao Luo ◽  
Wenchang Lv ◽  
Weijie Hu ◽  
Chongru Zhao ◽  
...  

AbstractBreast cancer (BC) is the most frequently invasive malignancy and the leading cause of tumor-related mortality among women worldwide. Cancer metastasis is a complex, multistage process, which eventually causes tumor cells to colonize and grow at the metastatic site. Distant organ metastases are the major obstacles to the management of advanced BC patients. Notably, exosomes are defined as specialized membrane-enclosed extracellular vesicles with specific biomarkers, which are found in a wide variety of body fluids. Recent studies have demonstrated that exosomes are essential mediators in shaping the tumor microenvironment and BC metastasis. The transferred tumor-derived exosomes modify the capability of invasive behavior and organ-specific metastasis in recipient cells. BC exosomal components, mainly including noncoding RNAs (ncRNAs), proteins, lipids, are the most investigated components in BC metastasis. In this review, we have emphasized the multifaceted roles and mechanisms of tumor-derived exosomes in BC metastasis based on these important components. The underlying mechanisms mainly include the invasion behavior change, tumor vascularization, the disruption of the vascular barrier, and the colonization of the targeted organ. Understanding the significance of tumor-derived exosomal components in BC metastasis is critical for yielding novel routes of BC intervention.


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