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- W4294884815 abstract "Brain metastasis is a complication of increasing incidence in patients with breast cancer at advanced disease stage. It is a severe condition characterized by a rapid decline in quality of life and poor prognosis. There is a critical clinical need to develop effective therapies to prevent and treat brain metastases. Here, we describe a unique and robust spontaneous preclinical model of breast cancer metastasis to the brain (4T1-BM 2 ) in mice that has been instrumental in uncovering molecular mechanisms guiding metastatic dissemination and colonization of the brain. Key experimental findings were validated in the additional murine D2A1-BM 2 model and in human MDA231-BrM 2 model. Gene expression analyses and functional studies, coupled with clinical transcriptomic and histopathological investigations, identified connexins (Cxs) and focal adhesion kinase (FAK) as master molecules orchestrating breast cancer colonization of the brain. Cx31 promoted homotypic tumor cell adhesion, heterotypic tumor-astrocyte interaction, and FAK phosphorylation. FAK signaling prompted NF-κB activation inducing Lamc2 expression and laminin 332 (laminin 5) deposition, α6 integrin–mediated adhesion, and sustained survival and growth within brain parenchyma. In the MDA231-BrM 2 model, the human homologous molecules CX43, LAMA4, and α3 integrin were involved. Systemic treatment with FAK inhibitors reduced brain metastasis progression. In conclusion, we report a spontaneous model of breast cancer metastasis to the brain and identified Cx-mediated FAK–NF-κB signaling as a mechanism promoting cell-autonomous and microenvironmentally controlled cell survival for brain colonization. Considering the limited therapeutic options for brain metastatic disease in cancer patients, we propose FAK as a therapeutic candidate to further pursue in the clinic." @default.
- W4294884815 created "2022-09-07" @default.
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- W4294884815 date "2022-09-07" @default.
- W4294884815 modified "2023-10-18" @default.
- W4294884815 title "Connexins orchestrate progression of breast cancer metastasis to the brain by promoting FAK activation" @default.
- W4294884815 cites W121395170 @default.
- W4294884815 cites W1581002015 @default.
- W4294884815 cites W1593681564 @default.
- W4294884815 cites W1601529652 @default.
- W4294884815 cites W1980139100 @default.
- W4294884815 cites W1982252520 @default.
- W4294884815 cites W1985830678 @default.
- W4294884815 cites W1993022928 @default.
- W4294884815 cites W1997782804 @default.
- W4294884815 cites W2009134006 @default.
- W4294884815 cites W2012347139 @default.
- W4294884815 cites W2017773820 @default.
- W4294884815 cites W2023291646 @default.
- W4294884815 cites W2025534439 @default.
- W4294884815 cites W2034443097 @default.
- W4294884815 cites W2039471255 @default.
- W4294884815 cites W2041617023 @default.
- W4294884815 cites W2043166238 @default.
- W4294884815 cites W2043686550 @default.
- W4294884815 cites W2044423100 @default.
- W4294884815 cites W2051831012 @default.
- W4294884815 cites W2057151160 @default.
- W4294884815 cites W2058689904 @default.
- W4294884815 cites W2081098333 @default.
- W4294884815 cites W2084544728 @default.
- W4294884815 cites W2089747862 @default.
- W4294884815 cites W2096283457 @default.
- W4294884815 cites W2097672819 @default.
- W4294884815 cites W2103071425 @default.
- W4294884815 cites W2109972881 @default.
- W4294884815 cites W2115260093 @default.
- W4294884815 cites W2123232388 @default.
- W4294884815 cites W2125782175 @default.
- W4294884815 cites W2133286757 @default.
- W4294884815 cites W2135944976 @default.
- W4294884815 cites W2137028370 @default.
- W4294884815 cites W2145990138 @default.
- W4294884815 cites W2146875866 @default.
- W4294884815 cites W2150737519 @default.
- W4294884815 cites W2158186154 @default.
- W4294884815 cites W2166618447 @default.
- W4294884815 cites W2166659170 @default.
- W4294884815 cites W2175940415 @default.
- W4294884815 cites W2283853409 @default.
- W4294884815 cites W2395943362 @default.
- W4294884815 cites W2464706565 @default.
- W4294884815 cites W2558947257 @default.
- W4294884815 cites W2591646072 @default.
- W4294884815 cites W2616126700 @default.
- W4294884815 cites W2736010006 @default.
- W4294884815 cites W2740569386 @default.
- W4294884815 cites W2767057706 @default.
- W4294884815 cites W2785091318 @default.
- W4294884815 cites W2875176358 @default.
- W4294884815 cites W2885053311 @default.
- W4294884815 cites W2896823377 @default.
- W4294884815 cites W2912663500 @default.
- W4294884815 cites W2917035470 @default.
- W4294884815 cites W2917772946 @default.
- W4294884815 cites W2940057770 @default.
- W4294884815 cites W2952481429 @default.
- W4294884815 cites W2981197192 @default.
- W4294884815 cites W2994525341 @default.
- W4294884815 cites W2995808512 @default.
- W4294884815 cites W3006930853 @default.
- W4294884815 cites W3007573818 @default.
- W4294884815 cites W3011990562 @default.
- W4294884815 cites W3025134199 @default.
- W4294884815 cites W3040944544 @default.
- W4294884815 cites W3109175864 @default.
- W4294884815 cites W3115960961 @default.
- W4294884815 cites W3116476506 @default.
- W4294884815 cites W3135580847 @default.
- W4294884815 cites W3181129406 @default.
- W4294884815 cites W3190184148 @default.
- W4294884815 cites W37428664 @default.
- W4294884815 cites W4200374936 @default.
- W4294884815 cites W4200592593 @default.