DJ-1 promotes epithelial-to-mesenchymal transition via enhancing FGF9 expression in colorectal cancer
Tumor metastasis is the main contributor to high recurrence and mortality in colorectal cancer (CRC). In a previous study, we found that DJ-1 plays an important role in CRC metastasis, and is the main target in Ciclopirox olamine (CPX)-treated CRC. However, the mechanism underlying DJ-1-induced CRC...
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doaj-c76b40a8451f4f89b906afb30b6ba7ba2021-06-02T19:00:36ZengThe Company of BiologistsBiology Open2046-63902020-05-019510.1242/bio.051680051680DJ-1 promotes epithelial-to-mesenchymal transition via enhancing FGF9 expression in colorectal cancerLonghao Li0Chundong Zhang1Yi Li2Ying Zhang3Yunlong Lei4 Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China Department of Biochemistry and Molecular Biology, and Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China Department of Biochemistry and Molecular Biology, and Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China Department of Biochemistry and Molecular Biology, and Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China Department of Biochemistry and Molecular Biology, and Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, China Tumor metastasis is the main contributor to high recurrence and mortality in colorectal cancer (CRC). In a previous study, we found that DJ-1 plays an important role in CRC metastasis, and is the main target in Ciclopirox olamine (CPX)-treated CRC. However, the mechanism underlying DJ-1-induced CRC metastasis remains elusive. In the present study, our results showed that DJ-1 could activate Wnt signaling resulting in enhanced invasive potential and epithelial-to-mesenchymal transition (EMT) in CRC cells. RNA-seq and bioinformatics analysis reveals that the DJ-1/Wnt signaling pathway may promote CRC cells’ EMT by regulating fibroblast growth factor 9 (FGF9) expression. Molecular validation showed that expression of FGF9 was upregulated by the DJ-1/Wnt signaling pathway and decreasing FGF9-expression impeded DJ-1-induced CRC invasive ability and EMT, suggesting that FGF9 is involved in DJ-1-enhanced CRC metastasis. In addition, we show that FGF9 was overexpressed in CRC human specimens and was significantly associated with tumor differentiation. High FGF9 expression was correlated with worse overall survival, and a correlation exhibited between FGF9 and EMT markers (E-cadherin and Vimentin) in CRC samples. Together, our results determined that FGF9 was involved in DJ-1-induced invasion and EMT in CRC cells, and may represent a promising therapeutic candidate for CRC anti-metastatic strategies.http://bio.biologists.org/content/9/5/bio051680colorectal cancerdj-1fgf9emt |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Longhao Li Chundong Zhang Yi Li Ying Zhang Yunlong Lei |
spellingShingle |
Longhao Li Chundong Zhang Yi Li Ying Zhang Yunlong Lei DJ-1 promotes epithelial-to-mesenchymal transition via enhancing FGF9 expression in colorectal cancer Biology Open colorectal cancer dj-1 fgf9 emt |
author_facet |
Longhao Li Chundong Zhang Yi Li Ying Zhang Yunlong Lei |
author_sort |
Longhao Li |
title |
DJ-1 promotes epithelial-to-mesenchymal transition via enhancing FGF9 expression in colorectal cancer |
title_short |
DJ-1 promotes epithelial-to-mesenchymal transition via enhancing FGF9 expression in colorectal cancer |
title_full |
DJ-1 promotes epithelial-to-mesenchymal transition via enhancing FGF9 expression in colorectal cancer |
title_fullStr |
DJ-1 promotes epithelial-to-mesenchymal transition via enhancing FGF9 expression in colorectal cancer |
title_full_unstemmed |
DJ-1 promotes epithelial-to-mesenchymal transition via enhancing FGF9 expression in colorectal cancer |
title_sort |
dj-1 promotes epithelial-to-mesenchymal transition via enhancing fgf9 expression in colorectal cancer |
publisher |
The Company of Biologists |
series |
Biology Open |
issn |
2046-6390 |
publishDate |
2020-05-01 |
description |
Tumor metastasis is the main contributor to high recurrence and mortality in colorectal cancer (CRC). In a previous study, we found that DJ-1 plays an important role in CRC metastasis, and is the main target in Ciclopirox olamine (CPX)-treated CRC. However, the mechanism underlying DJ-1-induced CRC metastasis remains elusive. In the present study, our results showed that DJ-1 could activate Wnt signaling resulting in enhanced invasive potential and epithelial-to-mesenchymal transition (EMT) in CRC cells. RNA-seq and bioinformatics analysis reveals that the DJ-1/Wnt signaling pathway may promote CRC cells’ EMT by regulating fibroblast growth factor 9 (FGF9) expression. Molecular validation showed that expression of FGF9 was upregulated by the DJ-1/Wnt signaling pathway and decreasing FGF9-expression impeded DJ-1-induced CRC invasive ability and EMT, suggesting that FGF9 is involved in DJ-1-enhanced CRC metastasis. In addition, we show that FGF9 was overexpressed in CRC human specimens and was significantly associated with tumor differentiation. High FGF9 expression was correlated with worse overall survival, and a correlation exhibited between FGF9 and EMT markers (E-cadherin and Vimentin) in CRC samples. Together, our results determined that FGF9 was involved in DJ-1-induced invasion and EMT in CRC cells, and may represent a promising therapeutic candidate for CRC anti-metastatic strategies. |
topic |
colorectal cancer dj-1 fgf9 emt |
url |
http://bio.biologists.org/content/9/5/bio051680 |
work_keys_str_mv |
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