Journal ArticleDOI
Differential effects on lung and bone metastasis of breast cancer by Wnt signalling inhibitor DKK1
Xueqian Zhuang,Hao Zhang,Xiaoyan Li,Xiaoxun Li,Min Cong,Fangli Peng,Jingyi Yu,Xingwang Zhang,Qifeng Yang,Guohong Hu +9 more
TLDR
It is shown that tumour-secreted DKK1 is a serological marker of breast cancer metastasis organotropism and inhibits lung metastasis and provides a rationale for new anti-metastasis approaches.Abstract:
Metastatic cancer is a systemic disease, and metastasis determinants might elicit completely different effects in various target organs. Here we show that tumour-secreted DKK1 is a serological marker of breast cancer metastasis organotropism and inhibits lung metastasis. DKK1 suppresses PTGS2-induced macrophage and neutrophil recruitment in lung metastases by antagonizing cancer cell non-canonical WNT/PCP-RAC1-JNK signalling. In the lungs, DKK1 also inhibits WNT/Ca2+-CaMKII-NF-κB signalling and suppresses LTBP1-mediated TGF-β secretion of cancer cells. In contrast, DKK1 promotes breast-to-bone metastasis by regulating canonical WNT signalling of osteoblasts. Importantly, targeting canonical WNT may not be beneficial to treatment of metastatic cancer, while combinatory therapy against JNK and TGF-β signalling effectively prevents metastasis to both the lungs and bone. Thus, DKK1 represents a class of Janus-faced molecules with dichotomous roles in organotropic metastasis, and our data provide a rationale for new anti-metastasis approaches.read more
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TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis
TL;DR: The role of TGF-β signaling in cell cycle arrest, apoptosis, EMT and cancer cell metastasis is considered and recent insights into the multistep and dynamically controlled process of T GF-β-induced EMT are highlighted.
Journal ArticleDOI
Defining the Hallmarks of Metastasis
Danny R. Welch,Douglas R. Hurst +1 more
TL;DR: By defining these first principles of metastasis, this review identifies four distinguishing features that are required: motility and invasion, ability to modulate the secondary site or local microenvironments, plasticity, and ability to colonize secondary tissues.
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Metastatic heterogeneity of breast cancer: Molecular mechanism and potential therapeutic targets.
TL;DR: The potential of identifying specific molecules against tumor cells or tumor microenvironments to thwart the development of metastatic disease and improve the prognosis of breast cancer patients is discussed.
早期関節リウマチ:brief overview
TL;DR: In this article, the authors describe a window of opportunity for window-of-opportunity, where the window is a window-window of opportunity window for a specific target.
Journal ArticleDOI
Organotropism: new insights into molecular mechanisms of breast cancer metastasis.
TL;DR: The molecular mechanisms of breast cancer organotropic metastasis are summarized by focusing on tumor cell molecular alterations, stemness features, and cross-talk with the host environment.
References
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