Journal Article

DKFZ-2021-01628

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png JUNB suppresses distant metastasis by influencing the initial metastatic stage.

Wutschka, J. (First author)DKFZ* ; Kast, B.DKFZ* ; Sator-Schmitt, M.DKFZ* ; Appak-Baskoy, S.DKFZ* ; Hess, J.DKFZ* ; Sinn, H.-P. ; Angel, P.DKFZ* ; Schorpp-Kistner, M. (Last author)DKFZ*

2021
Springer Science + Business Media B.V. Dordrecht

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Please use a persistent id in citations: doi:10.1007/s10585-021-10108-9

Abstract: The 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.

Keyword(s): Metastasis ; Transcription factor ; Tumor microenvironment

Note: DKFZ-ZMBH Alliance / #EA:A100#LA:A100#/ 2021 Aug;38(4):411-423

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Contributing Institute(s):

1. A100 Signaltransduktion/ Wachstumskontrolle (A100)
2. E221 AG Molekulare Grundlagen von HNO-Tumoren (E221)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Essential Science Indicators ; IF < 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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