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000169894 041__ $$aEnglish
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000169894 1001_ $$0P:(DE-He78)86ebb8b048c77e1c7eff002af09c229f$$aWutschka, Juliane$$b0$$eFirst author$$udkfz
000169894 245__ $$aJUNB suppresses distant metastasis by influencing the initial metastatic stage.
000169894 260__ $$aDordrecht$$bSpringer Science + Business Media B.V.$$c2021
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000169894 500__ $$aDKFZ-ZMBH Alliance / #EA:A100#LA:A100#/ 2021 Aug;38(4):411-423
000169894 520__ $$aThe complex interactions between cells of the tumor microenvironment and cancer cells are considered a major determinant of cancer progression and metastasis. Yet, our understanding of the mechanisms of metastatic disease is not sufficient to successfully treat patients with advanced-stage cancer. JUNB is a member of the AP-1 transcription factor family shown to be frequently deregulated in human cancer and associated with invasion and metastasis. A strikingly high stromal JUNB expression in human breast cancer samples prompted us to functionally investigate the consequences of JUNB loss in cells of the tumor microenvironment on cancer progression and metastasis in mice. To adequately mimic the clinical situation, we applied a syngeneic spontaneous breast cancer metastasis model followed by primary tumor resection and identified stromal JUNB as a potent suppressor of distant metastasis. Comprehensive characterization of the JUNB-deficient tumor microenvironment revealed a strong influx of myeloid cells into primary breast tumors and lungs at early metastatic stage. In these infiltrating neutrophils, BV8 and MMP9, proteins promoting angiogenesis and tissue remodeling, were specifically upregulated in a JUNB-dependent manner. Taken together, we established stromal JUNB as a strong suppressor of distant metastasis. Consequently, therapeutic strategies targeting AP-1 should be carefully designed not to interfere with stromal JUNB expression as this may be detrimental for cancer patients.
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000169894 650_7 $$2Other$$aMetastasis
000169894 650_7 $$2Other$$aTranscription factor
000169894 650_7 $$2Other$$aTumor microenvironment
000169894 7001_ $$0P:(DE-He78)417337e7f94f6e1325a168191cbdc4f1$$aKast, Bettina$$b1$$udkfz
000169894 7001_ $$0P:(DE-He78)2119821cf3458781f06157c7aeecba8b$$aSator-Schmitt, Melanie$$b2$$udkfz
000169894 7001_ $$0P:(DE-He78)ac5b93418fe9d72f17cb5e424ea778b8$$aAppak-Baskoy, Sila$$b3
000169894 7001_ $$0P:(DE-He78)2e5f34f1c58eda4787a14c9dc139ca5f$$aHess, Jochen$$b4$$udkfz
000169894 7001_ $$aSinn, Hans-Peter$$b5
000169894 7001_ $$0P:(DE-He78)f4f068e71e0d87bf0ad51e6214ab84e9$$aAngel, Peter$$b6$$udkfz
000169894 7001_ $$0P:(DE-He78)b64b20197abce42e40bbc84a22b9ca62$$aSchorpp-Kistner, Marina$$b7$$eLast author$$udkfz
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