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Human breast cancer-associated fibroblasts enhance cancer cell proliferation through increased TGF-α cleavage by ADAM17

Authors
 Ming-Qing Gao  ;  Baek Gil Kim  ;  Suki Kang  ;  Yoon Pyo Choi  ;  Joo-Heon Yoon  ;  Nam Hoon Cho 
Citation
 CANCER LETTERS, Vol.336(1) : 240-246, 2013 
Journal Title
 CANCER LETTERS 
ISSN
 0304-3835 
Issue Date
2013
Keywords
ADAM17 ; Breast cancer ; Cancer-associated fibroblasts ; TGF-α ; Cell proliferation
Abstract
We demonstrate here increased expression of ADAM17 protein in cancer-associated fibroblasts (CAFs) extracted from human breast carcinomas compared with donor-matched normal fibroblasts, and TGF-α secretion positively correlates with ADAM17 expression in these cells. In SK-BR-3 cells co-cultured with CAFs, CAF-secreted TGF-α promotes cell proliferation by activation of EGFR, Akt, and ERK, but it does not promote cell migration. Furthermore, anti-TGF-α neutralizing antibodies antagonize the CAF-dependent increase in proliferation and activation of EGFR, Akt and ERK. Thus, pharmacologic inhibition of ADAM17 and TGF-α may have therapeutic potential for the treatment of breast cancer when fibroblast-directed therapy is considered.
Full Text
http://www.sciencedirect.com/science/article/pii/S0304383513003807
DOI
10.1016/j.canlet.2013.05.011
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
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
Gao, Ming Qing(고명청)
Kim, Baek Gil(김백길) ORCID logo https://orcid.org/0000-0001-6270-1433
Yoon, Joo Heon(윤주헌)
Cho, Nam Hoon(조남훈) ORCID logo https://orcid.org/0000-0002-0045-6441
Choi, Yoon Pyo(최윤표)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87065
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