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ITGB4-mediated metabolic reprogramming of cancer-associated fibroblasts

Authors
 Jin Sol Sung  ;  Chan Woo Kang  ;  Suki Kang  ;  Yeonsue Jang  ;  Young Chan Chae  ;  Baek Gil Kim  ;  Nam Hoon Cho 
Citation
 ONCOGENE, Vol.39(3) : 664-676, 2020 
Journal Title
 ONCOGENE 
ISSN
 0950-9232 
Issue Date
2020
Abstract
Integrin beta 4 (ITGB4) overexpression in cancer cells contributes to cancer progression. However, the role of stromal ITGB4 expression in cancer progression remains poorly understood, despite stromal ITGB4 overexpression in malignant cancers. In our study, ITGB4-overexpressing triple negative breast cancer (TNBC) cells provided cancer-associated fibroblasts (CAFs) with ITGB4 proteins via exosomes, which induced BNIP3L-dependent mitophagy and lactate production in CAFs. In coculture assays, the ITGB4-induced mitophagy and glycolysis were suppressed in CAFs by knocking down ITGB4 or inhibiting exosome generation in MDA-MB-231, or blocking c-Jun or AMPK phosphorylation in CAFs. ITGB4-overexpressing CAF-conditioned medium promoted the proliferation, epithelial-to-mesenchymal transition, and invasion of breast cancer cells. In a co-transplant mouse model, MDA-MB-231 made a bigger tumor mass with CAFs than ITGB4 knockdown MDA-MB-231. Herein, we presented how TNBC-derived ITGB4 protein triggers glycolysis in CAFs via BNIP3L-dependent mitophagy and suggested the possibility that ITGB4-induced mitophagy could be targeted as a cancer therapy.
Full Text
https://www.nature.com/articles/s41388-019-1014-0
DOI
10.1038/s41388-019-1014-0
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Suki(강숙희) ORCID logo https://orcid.org/0000-0002-9957-3479
Kim, Baek Gil(김백길) ORCID logo https://orcid.org/0000-0001-6270-1433
Jang, Yeon Sue(장연수) ORCID logo https://orcid.org/0000-0001-5683-0001
Cho, Nam Hoon(조남훈) ORCID logo https://orcid.org/0000-0002-0045-6441
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/174821
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