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

2020 ◽  
Vol 11 (1) ◽  
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.

scholarly journals Clinical Impact of Sphingosine-1-Phosphate in Breast Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
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.

Thidiazuron suppresses breast cancer progression via targeting miR-132 and miR-202-5p/PTEN axis mediated dysregulation of PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
Hairul-Islam Ibrahim ◽  
Mohammad Bani Ismail ◽  
Rebai Ben Ammar ◽  
Emad Ahmed
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Metastatic Cancer ◽  
Akt Signaling ◽  
Breast Cancer Metastasis ◽  
Akt Signaling Pathway ◽  
Stressful Environment

Chemo-resistance and metastatic disease development are the most common causes of breast cancer recurrence and death. Thidiazuron (TDZ) is a plant growth regulator, its biological role on human and animals has not been yet clarified. In the present study, we investigated the anticancer activity of this plant phytohormone on the drug resistant-triple negative breast cancer MDA-MB-231 cell line. Treatment of the breast cancer cells with TDZ (1-50 μM) caused more stressful environment and induced a significant increase in percentages of active caspases positive cells. In addition, TDZ treatment (5 and 10 μM) significantly attenuated the migration and the invasion activities of these highly metastatic cancer cells. Mechanistically, TDZ reducesd cancer progression and invasive activity through targeting miR-202-5p, which stimulatesd the expression of the phosphatase and tensin homolog (PTEN), the tumor suppressor that downregulates PI3K/AKT signaling pathway. In the meantime, TDZ treatment statistically upregulatesd the suppressor of breast cancer proliferation, miRNA-132 that is also implicated in dysregulating the TEN-AKT/the nuclear factor NFκB signaling pathway. Interestingly, our molecular docking analysis revealed potential non-covalent interaction between TDZ with AKT, PTEN and PI3K. These findings suggest that TDZ may suppresses breast cancer metastasis through targeting miRNA-132, miR-202-5p/PTEN and PI3K/AKT downstream molecules.

scholarly journals The IKK/NF-κB signaling pathway requires Morgana to drive breast cancer metastasis

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Federica Fusella ◽  
Laura Seclì ◽  
Elena Busso ◽  
Anna Krepelova ◽  
Enrico Moiso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis

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

Cancers ◽  
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.

scholarly journals AKR1B10 promotes breast cancer metastasis through integrin α5/δ-catenin mediated FAK/Src/Rac1 signaling pathway

Oncotarget ◽  
2016 ◽  
Vol 7 (28) ◽  
pp. 43779-43791 ◽  
Author(s):  
Chenfei Huang ◽  
Steven Verhulst ◽  
Yi Shen ◽  
Yiwen Bu ◽  
Yu Cao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Integrin Α5
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