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CXCL5/ENA78 increased cell migration and epithelial‐to‐mesenchymal transition of hormone‐independent prostate cancer by early growth response‐1/snail signaling pathway
Author(s) -
Kuo PoLin,
Chen YenHsu,
Chen TunChieh,
Shen KunHung,
Hsu YaLing
Publication year - 2011
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22445
Subject(s) - du145 , prostate cancer , cancer research , cell growth , cxcl5 , mapk/erk pathway , downregulation and upregulation , biology , snail , epithelial–mesenchymal transition , medicine , signal transduction , chemistry , cancer , microbiology and biotechnology , metastasis , lncap , receptor , biochemistry , ecology , chemokine , gene
Prostate cancers that are resistant to hormone therapy are more invasive and have greater ability to spread to other organs than androgen‐dependent prostate cancers. Furthermore, this type of prostate cancer is also highly resistant to current forms of chemotherapy. This study analyzed CXCL5/ENA78, which is highly expressed in androgen‐independent prostate cancers, and is responsible for cell migration and epithelial‐to‐mesenchymal transition in two androgen‐independent prostate cancer cell lines. Inducement of PC‐3 and DU145 cancer progression by CXCL5/ENA78 is associated with increased Raf/MEK/ERK activation, and the upregulation of early growth response‐1 (Egr‐1) and Snail. Blockade of Egr‐1 decreased Snail upregulation and cell migration, indicating that Egr‐1 is required in CXCL5/ENA78‐mediated Snail enhancement and cell migration. In addition, Egr‐1 siRNA also decreased the effect of CXCL5/ENA78 on p27 inhibition, Cdk4 induction and cell proliferation, suggesting Egr‐1 is also involved in CXCL5/ENA78‐mediated cell growth. Moreover, blocking ERK1/2 by siRNA suppressed CXCL5/ENA78‐induced Egr‐1 enhancement, cell migration, and proliferation. Our study suggests that inhibition of CXCL5/ENA78‐mediated ERK/Egr‐1/Snail signaling is an attractive therapeutic target for androgen‐independent prostate cancer. J. Cell. Physiol. 226: 1224–1231, 2011. © 2010 Wiley‐Liss, Inc.