Tumor-derived exosomal components: the multifaceted roles and mechanisms in breast cancer metastasis

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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A Role for Epigenetic Mechanisms in Organ-Specific Breast Cancer Metastasis

10.21236/ada536747 ◽

2010 ◽

Author(s):

Mi Y. Kim

Keyword(s):

Breast Cancer ◽

Cancer Metastasis ◽

Breast Cancer Metastasis ◽

Epigenetic Mechanisms ◽

Organ Specific

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Clinical Impact of Sphingosine-1-Phosphate in Breast Cancer

Mediators of Inflammation ◽

10.1155/2017/2076239 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 15

Author(s):

Junko Tsuchida ◽

Masayuki Nagahashi ◽

Kazuaki Takabe ◽

Toshifumi Wakai

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Cancer Metastasis ◽

Clinical Importance ◽

Breast Cancer Metastasis ◽

Lipid Mediator ◽

Breast Cancer Patients ◽

Cellular Functions ◽

Sphingosine 1 Phosphate ◽

Underlying Mechanisms

Breast cancer metastasizes to lymph nodes or other organs, which determine the prognosis of patients. It is difficult to cure the breast cancer patients with distant metastasis due to resistance to drug therapies. Elucidating the underlying mechanisms of breast cancer metastasis and drug resistance is expected to provide new therapeutic targets. Sphingosine-1-phosphate (S1P) is a pleiotropic, bioactive lipid mediator that regulates many cellular functions, including proliferation, migration, survival, angiogenesis/lymphangiogenesis, and immune responses. S1P is formed in cells by sphingosine kinases and released from them, which acts in an autocrine, paracrine, and/or endocrine manner. S1P in extracellular space, such as interstitial fluid, interacts with components in the tumor microenvironment, which may be important for metastasis. Importantly, recent translational research has demonstrated an association between S1P levels in breast cancer patients and clinical outcomes, highlighting the clinical importance of S1P in breast cancer. We suggest that S1P is one of the key molecules to overcome the resistance to the drug therapies, such as hormonal therapy, anti-HER2 therapy, or chemotherapy, all of which are crucial aspects of a breast cancer treatment.

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

Cancer Letters ◽

10.1016/j.canlet.2020.07.042 ◽

2020 ◽

Vol 493 ◽

pp. 41-54

Author(s):

Jiang Ren ◽

Yanhong Wang ◽

Thomas Ware ◽

Josephine Iaria ◽

Peter ten Dijke ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Metastasis ◽

Mek Inhibitor ◽

Breast Cancer Metastasis ◽

Bmp Signaling ◽

Organ Specific

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Ketohexokinase-A acts as a nuclear protein kinase that mediates fructose-induced metastasis in breast cancer

Nature Communications ◽

10.1038/s41467-020-19263-1 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 3

Author(s):

Jiyoung Kim ◽

Jengmin Kang ◽

Ye-Lim Kang ◽

Jongmin Woo ◽

Youngsoo Kim ◽

...

Keyword(s):

Breast Cancer ◽

Signaling Pathway ◽

Cancer Metastasis ◽

Breast Cancer Metastasis ◽

Fructose Intake ◽

High Fructose ◽

Underlying Mechanisms ◽

Necessary And Sufficient ◽

Therapeutic Perspective ◽

Harmful Effects

Abstract Harmful effects of high fructose intake on health have been widely reported. Although fructose is known to promote cancer, little is known about the underlying mechanisms. Here, we found that fructose triggers breast cancer metastasis through the ketohexokinase-A signaling pathway. Molecular experiments showed that ketohexokinase-A, rather than ketohexokinase-C, is necessary and sufficient for fructose-induced cell invasion. Ketohexokinase-A-overexpressing breast cancer was found to be highly metastatic in fructose-fed mice. Mechanistically, cytoplasmic ketohexokinase-A enters into the nucleus during fructose stimulation, which is mediated by LRRC59 and KPNB1. In the nucleus, ketohexokinase-A phosphorylates YWHAH at Ser25 and the YWHAH recruits SLUG to the CDH1 promoter, which triggers cell migration. This study provides the effect of nutrition on breast cancer metastasis. High intake of fructose should be restricted in cancer patients to reduce the risk of metastasis. From a therapeutic perspective, the ketohexokinase-A signaling pathway could be a potential target to prevent cancer metastasis.

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A Methodological Approach to Unravel Organ-Specific Breast Cancer Metastasis

Journal of Mammary Gland Biology and Neoplasia ◽

10.1007/s10911-012-9256-2 ◽

2012 ◽

Vol 17 (2) ◽

pp. 135-145 ◽

Cited By ~ 6

Author(s):

Sébastien Nola ◽

Soraya Sin ◽

Florian Bonin ◽

Rosette Lidereau ◽

Keltouma Driouch

Keyword(s):

Breast Cancer ◽

Cancer Metastasis ◽

Methodological Approach ◽

Breast Cancer Metastasis ◽

Organ Specific

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Combination of Mitochondrial Targeting Doxorubicin with Bcl-2 Function Converting Peptide NuBCP-9 for Synergistic Breast Cancer Metastasis Inhibition

Journal of Materials Chemistry B ◽

10.1039/d0tb02564j ◽

2021 ◽

Author(s):

Jiatao Yang ◽

Qiuyi Li ◽

Rui Zhou ◽

Minglu Zhou ◽

Xi Lin ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Metastasis ◽

Cancer Metastasis ◽

Breast Cancer Metastasis ◽

Breast Cancer Patients ◽

Mitochondrial Targeting ◽

Distant Organ Metastasis ◽

Metastasis Inhibition ◽

Organ Metastasis ◽

Distant Organ

Distant organ metastasis is the main cause of death in breast cancer patients. Evidences have shown that mitochondria also play a crucial role in tumor metastasis, except for as apoptosis...

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Tiny miRNAs Play a Big Role in the Treatment of Breast Cancer Metastasis

Cancers ◽

10.3390/cancers13020337 ◽

2021 ◽

Vol 13 (2) ◽

pp. 337

Author(s):

Andrea York Tiang Teo ◽

Xiaoqiang Xiang ◽

Minh TN Le ◽

Andrea Li-Ann Wong ◽

Qi Zeng ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Tumour Progression ◽

Tumour Microenvironment ◽

Breast Cancer Metastasis ◽

Metastatic Progression ◽

Mesenchymal Transition ◽

Recent Developments ◽

Underlying Mechanisms

Distant organ metastases accounts for the majority of breast cancer deaths. Given the prevalence of breast cancer in women, it is imperative to understand the underlying mechanisms of its metastatic progression and identify potential targets for therapy. Since their discovery in 1993, microRNAs (miRNAs) have emerged as important regulators of tumour progression and metastasis in various cancers, playing either oncogenic or tumour suppressor roles. In the following review, we discuss the roles of miRNAs that potentiate four key areas of breast cancer metastasis—angiogenesis, epithelial-mesenchymal transition, the Warburg effect and the tumour microenvironment. We then evaluate the recent developments in miRNA-based therapies in breast cancer, which have shown substantial promise in controlling tumour progression and metastasis. Yet, certain challenges must be overcome before these strategies can be implemented in clinical trials.

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