DCBLD2 Mediates Epithelial-Mesenchymal Transition-Induced Metastasis by Cisplatin in Lung Adenocarcinoma
Growing evidence suggests that cisplatin and other chemotherapeutic agents promote tumor metastasis while inhibiting tumor growth, which is a critical issue for certain patients in clinical practices. However, the role of chemotherapeutics in promoting tumor metastasis and the molecular mechanism in...
Main Authors: | , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2021-03-01
|
Series: | Cancers |
Subjects: | |
Online Access: | https://www.mdpi.com/2072-6694/13/6/1403 |
id |
doaj-02d3a07449b6478b96721c6dd09fb9f7 |
---|---|
record_format |
Article |
spelling |
doaj-02d3a07449b6478b96721c6dd09fb9f72021-03-20T00:03:42ZengMDPI AGCancers2072-66942021-03-01131403140310.3390/cancers13061403DCBLD2 Mediates Epithelial-Mesenchymal Transition-Induced Metastasis by Cisplatin in Lung AdenocarcinomaXiaosu Chen0Yajing Lv1Kejia Xu2Xiaoshuang Wang3Yujia Zhao4Jia Li5Xuan Qin6Yi Shi7Longlong Wang8Antao Chang9Chongbiao Huang10Rong Xiang11The School of Medicine, Nankai University, Tianjin 300071, ChinaThe School of Medicine, Nankai University, Tianjin 300071, ChinaThe School of Medicine, Nankai University, Tianjin 300071, ChinaThe School of Medicine, Nankai University, Tianjin 300071, ChinaThe School of Medicine, Nankai University, Tianjin 300071, ChinaThe School of Medicine, Nankai University, Tianjin 300071, ChinaThe School of Medicine, Nankai University, Tianjin 300071, ChinaThe School of Medicine, Nankai University, Tianjin 300071, ChinaThe School of Medicine, Nankai University, Tianjin 300071, ChinaThe School of Medicine, Nankai University, Tianjin 300071, ChinaDepartment of Thoracic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, ChinaThe School of Medicine, Nankai University, Tianjin 300071, ChinaGrowing evidence suggests that cisplatin and other chemotherapeutic agents promote tumor metastasis while inhibiting tumor growth, which is a critical issue for certain patients in clinical practices. However, the role of chemotherapeutics in promoting tumor metastasis and the molecular mechanism involved are unclear. Here, we investigated the roles of cisplatin in promoting tumor metastasis in lung adenocarcinoma (LUAD). We demonstrated that cisplatin promoted epithelial-mesenchymal transition (EMT), cell motility, and metastasis in vitro and in vivo. The bioinformatic analysis and molecular biology approaches also indicated that DCBLD2 (Discoidin, CUB and LCCL domain containing 2) is a key gene that mediates cisplatin-induced metastasis. DCBLD2 stabilizes β-catenin by phosphorylating GSK3β and transporting accumulated β-catenin to the nucleus to promote the expression of EMT-related transcriptional factors (TFs), ultimately resulting in tumor metastasis. We also identified that cisplatin enhanced DCBLD2 expression by phosphorylating ERK and hence the AP-1-driven transcription of DCBLD2. Furthermore, DCBLD2-specific siRNAs encapsulated by nanocarriers prominently inhibit cisplatin-induced metastasis in vivo. Therefore, DCBLD2 plays a key role in cisplatin-induced metastasis in LUAD and is a potential target for preventing chemotherapy-induced metastasis in vivo.https://www.mdpi.com/2072-6694/13/6/1403DCBLD2cisplatinepithelial-mesenchymal transition (EMT)metastasislung adenocarcinoma (LUAD) |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaosu Chen Yajing Lv Kejia Xu Xiaoshuang Wang Yujia Zhao Jia Li Xuan Qin Yi Shi Longlong Wang Antao Chang Chongbiao Huang Rong Xiang |
spellingShingle |
Xiaosu Chen Yajing Lv Kejia Xu Xiaoshuang Wang Yujia Zhao Jia Li Xuan Qin Yi Shi Longlong Wang Antao Chang Chongbiao Huang Rong Xiang DCBLD2 Mediates Epithelial-Mesenchymal Transition-Induced Metastasis by Cisplatin in Lung Adenocarcinoma Cancers DCBLD2 cisplatin epithelial-mesenchymal transition (EMT) metastasis lung adenocarcinoma (LUAD) |
author_facet |
Xiaosu Chen Yajing Lv Kejia Xu Xiaoshuang Wang Yujia Zhao Jia Li Xuan Qin Yi Shi Longlong Wang Antao Chang Chongbiao Huang Rong Xiang |
author_sort |
Xiaosu Chen |
title |
DCBLD2 Mediates Epithelial-Mesenchymal Transition-Induced Metastasis by Cisplatin in Lung Adenocarcinoma |
title_short |
DCBLD2 Mediates Epithelial-Mesenchymal Transition-Induced Metastasis by Cisplatin in Lung Adenocarcinoma |
title_full |
DCBLD2 Mediates Epithelial-Mesenchymal Transition-Induced Metastasis by Cisplatin in Lung Adenocarcinoma |
title_fullStr |
DCBLD2 Mediates Epithelial-Mesenchymal Transition-Induced Metastasis by Cisplatin in Lung Adenocarcinoma |
title_full_unstemmed |
DCBLD2 Mediates Epithelial-Mesenchymal Transition-Induced Metastasis by Cisplatin in Lung Adenocarcinoma |
title_sort |
dcbld2 mediates epithelial-mesenchymal transition-induced metastasis by cisplatin in lung adenocarcinoma |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-03-01 |
description |
Growing evidence suggests that cisplatin and other chemotherapeutic agents promote tumor metastasis while inhibiting tumor growth, which is a critical issue for certain patients in clinical practices. However, the role of chemotherapeutics in promoting tumor metastasis and the molecular mechanism involved are unclear. Here, we investigated the roles of cisplatin in promoting tumor metastasis in lung adenocarcinoma (LUAD). We demonstrated that cisplatin promoted epithelial-mesenchymal transition (EMT), cell motility, and metastasis in vitro and in vivo. The bioinformatic analysis and molecular biology approaches also indicated that DCBLD2 (Discoidin, CUB and LCCL domain containing 2) is a key gene that mediates cisplatin-induced metastasis. DCBLD2 stabilizes β-catenin by phosphorylating GSK3β and transporting accumulated β-catenin to the nucleus to promote the expression of EMT-related transcriptional factors (TFs), ultimately resulting in tumor metastasis. We also identified that cisplatin enhanced DCBLD2 expression by phosphorylating ERK and hence the AP-1-driven transcription of DCBLD2. Furthermore, DCBLD2-specific siRNAs encapsulated by nanocarriers prominently inhibit cisplatin-induced metastasis in vivo. Therefore, DCBLD2 plays a key role in cisplatin-induced metastasis in LUAD and is a potential target for preventing chemotherapy-induced metastasis in vivo. |
topic |
DCBLD2 cisplatin epithelial-mesenchymal transition (EMT) metastasis lung adenocarcinoma (LUAD) |
url |
https://www.mdpi.com/2072-6694/13/6/1403 |
work_keys_str_mv |
AT xiaosuchen dcbld2mediatesepithelialmesenchymaltransitioninducedmetastasisbycisplatininlungadenocarcinoma AT yajinglv dcbld2mediatesepithelialmesenchymaltransitioninducedmetastasisbycisplatininlungadenocarcinoma AT kejiaxu dcbld2mediatesepithelialmesenchymaltransitioninducedmetastasisbycisplatininlungadenocarcinoma AT xiaoshuangwang dcbld2mediatesepithelialmesenchymaltransitioninducedmetastasisbycisplatininlungadenocarcinoma AT yujiazhao dcbld2mediatesepithelialmesenchymaltransitioninducedmetastasisbycisplatininlungadenocarcinoma AT jiali dcbld2mediatesepithelialmesenchymaltransitioninducedmetastasisbycisplatininlungadenocarcinoma AT xuanqin dcbld2mediatesepithelialmesenchymaltransitioninducedmetastasisbycisplatininlungadenocarcinoma AT yishi dcbld2mediatesepithelialmesenchymaltransitioninducedmetastasisbycisplatininlungadenocarcinoma AT longlongwang dcbld2mediatesepithelialmesenchymaltransitioninducedmetastasisbycisplatininlungadenocarcinoma AT antaochang dcbld2mediatesepithelialmesenchymaltransitioninducedmetastasisbycisplatininlungadenocarcinoma AT chongbiaohuang dcbld2mediatesepithelialmesenchymaltransitioninducedmetastasisbycisplatininlungadenocarcinoma AT rongxiang dcbld2mediatesepithelialmesenchymaltransitioninducedmetastasisbycisplatininlungadenocarcinoma |
_version_ |
1724212413422632960 |