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EZH2 engages TGFβ signaling to promote breast cancer bone metastasis via integrin β1-FAK activation
Breast cancer cells are known to metastasize to the bone but why the cells should migrate and metastasize to this particular organ is not clearly understood. Here, the authors show that EZH2 activates an integrin B1 and FAK signaling pathway in breast cancer cells, which activates TGFB signaling to drive metastasis in the bone.
- Lin Zhang
- , Jingkun Qu
- & Dihua Yu
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Article
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Hypoxia-activated neuropeptide Y/Y5 receptor/RhoA pathway triggers chromosomal instability and bone metastasis in Ewing sarcoma
Ewing sarcoma tumour cells frequently metastasize to the bone but the molecular mechanisms governing this process are not well understood. Here, the authors show that neuropeptide Y/Y5 receptor pathway is activated in the hypoxic tumour microenvironment, which results in cytokinesis defects and chromosomal instability, leading to bone invasion.
- Congyi Lu
- , Akanksha Mahajan
- & Joanna Kitlinska
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Cooperative interaction between ERα and the EMT-inducer ZEB1 reprograms breast cancer cells for bone metastasis
The epithelial mesenchymal transition (EMT) is important in the metastatic spread of cancer cells. Here, the authors show that the EMT transcription factor, ZEB1, can modify estrogen receptor α during EMT and facilitate the migration of breast cancer cells to the bone
- Nastaran Mohammadi Ghahhari
- , Magdalena K. Sznurkowska
- & Didier Picard
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Article
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Engineered macrophages as near-infrared light activated drug vectors for chemo-photodynamic therapy of primary and bone metastatic breast cancer
Bone metastases are associated with poor prognosis in patients with breast cancer and limited therapeutic options. Here the authors exploit near-infrared light responsive macrophages for the tumor-selective delivery of oxaliplatin prodrug for chemo-photodynamic therapy of primary and bone metastatic breast cancer.
- Yanjuan Huang
- , Zilin Guan
- & Chunshun Zhao
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Article
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Acetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer
The therapies for bone metastatic prostate cancer are limited and the underlying mechanisms are unclear. Here, the authors show that bone derived TGF-β induces acetylation of KLF5 (Ac-KLF5), and Ac-KLF5 promotes prostate cancer bone metastasis and resistance to docetaxel by upregulating CXCR4.
- Baotong Zhang
- , Yixiang Li
- & Jin-Tang Dong
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Inter- and intra-tumor heterogeneity of metastatic prostate cancer determined by digital spatial gene expression profiling
The inter- and intra-tumor heterogeneity of metastatic prostate cancer (mPC) is underexplored. Here the authors use Digital Spatial Profiling to study gene and protein expression heterogeneity in 27 mPC patients, finding variation in associated pathways and potential immunotherapy targets.
- Lauren Brady
- , Michelle Kriner
- & Peter S. Nelson
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Differential regulation of breast cancer bone metastasis by PARP1 and PARP2
The effect of PARP inhibitors on bone mass and bone metastasis are unclear. Here, the authors show that PARP1/2 dual inhibitors may increase cancer bone metastasis through PARP2-dependent regulation of immature myeloid cells, and cause bone loss through PARP1/2-dependent regulation of osteoclasts.
- Hao Zuo
- , Dengbao Yang
- & Yihong Wan
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Article
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Microenvironmental IL1β promotes breast cancer metastatic colonisation in the bone via activation of Wnt signalling
In breast cancer, dormant cancer cells may develop into bone metastases. Here, the authors demonstrate that microenvironmental IL1β stimulates metastatic breast cancer cell colonisation in the bone via IL1β-NFKB/CREB-Wnt pathway activation and cancer stem cell colony formation
- Rachel Eyre
- , Denis G. Alférez
- & Robert B. Clarke
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Article
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A reliable murine model of bone metastasis by injecting cancer cells through caudal arteries
Reliably modelling bone metastasis in mice is essential for research. Here, the authors present a new murine model for cancer metastasis based on intra-caudal artery injection that reliably recapitulates bone metastasis.
- Takahiro Kuchimaru
- , Naoya Kataoka
- & Shinae Kizaka-Kondoh
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Article
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Bone-in-culture array as a platform to model early-stage bone metastases and discover anti-metastasis therapies
The bone microenvironment may alter therapeutic responses of disseminated breast cancer cells. Here the authors establish anex vivobone metastasis model, termed BICA, to delineate the effects of bone microenvironment and to rapidly discover anti-metastasis drugs.
- Hai Wang
- , Lin Tian
- & Xiang H.-F. Zhang
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Article
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MicroRNA-182 targets SMAD7 to potentiate TGFβ-induced epithelial-mesenchymal transition and metastasis of cancer cells
SMAD7 is a transcriptional target and a negative regulator of TGFβ signalling forming a negative feedback loop. Here the authors show that in cancer cells TGFβ activates the expression of microRNA-182 that suppresses SMAD7 protein, promoting TGFβ-mediated breast tumour invasion and bone metastasis.
- Jingyi Yu
- , Rong Lei
- & Guohong Hu
YAP silencing by RB1 mutation is essential for small-cell lung cancer metastasis