Bone morphogenetic protein 4 is overexpressed in and promotes migration and invasion of drug-resistant cancer cells.
Drug resistance and metastasis significantly hinder chemotherapy and worsen prognoses in cancer. Bone morphogenetic protein 4 (BMP4) belongs to the TGF-β superfamily, has broad biological activities in cell proliferation and cartilage differentiation and is also able to induce migration and invasion. Herein, we investigated the role of BMP4 in the regulation of metastasis in paclitaxel-resistant human esophageal carcinoma EC109 cells (EC109/Taxol) and docetaxel-resistant human gastric cancer MGC803 cells (MGC/Doc). In these drug-resistant cell lines, we found the cell motility was enhanced and BMP4 was up-regulated relative to their respective parental cell lines. Consistent with in vitro assays, migration potential and BMP4 expression were increased in EC109/Taxol nude mice. Furthermore, to address whether BMP4 was required to enhance the metastatic in EC109/Taxol cells, the pharmacological inhibitor of BMP signaling dorsomorphin was used; meanwhile, we found that the migration and invasion abilities were inhibited. Moreover, the canonical Smad signaling pathway was investigated. Overall, our studies demonstrated that BMP4 participates in the regulation of invasion and migration by EC109/Taxol cells, and inhibition of BMP4 may be a novel strategy to interfere with metastasis in cancer therapy.
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan 450001, PR China.
Kairui
K
Zhou
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan 450001, PR China.
Xiaoli
X
Shi
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan 450001, PR China.
Jinling
J
Huo
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan 450001, PR China.
Weihua
W
Liu
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan 450001, PR China.
Dongxiao
D
Yang
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan 450001, PR China.
Tengjiao
T
Yang
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan 450001, PR China.
Tiantian
T
Qin
School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, PR China; Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou, Henan 450001, PR China. Electronic address: wangcong@zzu.edu.cn.
Cong
C
Wang
D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051785:Smad Proteins / Q000378:metabolism
D055415:Bone Morphogenetic Protein 4; D051785:Smad Proteins
BMP4; Drug resistance; Esophagus cancer; Metastasis