Open AccessDDR1 promotes migration and invasion of breast cancer by modulating the Src-FAK signaling
Author(s) -
Qing Han,
Fei Xiao,
Lili Ma,
Jinyuan Zhou,
Lan Wang,
Huang Cheng,
Jianmin Zhu,
Fuli Yao,
Jianxin Lyu,
Linyong Du
Publication year - 2022
Publication title -
neoplasma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.628
H-Index - 50
eISSN - 1338-4317
pISSN - 0028-2685
DOI - 10.4149/neo_2022_220316n289
Subject(s) - ddr1 , breast cancer , cancer research , proto oncogene tyrosine protein kinase src , discoidin domain , metastasis , gene knockdown , cancer , cancer cell , medicine , biology , receptor , apoptosis , receptor tyrosine kinase , biochemistry
Breast cancer is the most commonly diagnosed cancer among women, causing 15% of patient deaths. The metastasis of breast cancer cells is the leading cause of death for patients. Several studies have shown that Discoidin Domain Receptor 1 (DDR1) was highly expressed in breast cancer and could influence tumor cell behaviors. However, the specific role of DDR1 in breast cancer metastasis is still elusive. In this study, we uncovered that DDR1 is significantly increased in breast cancer and inversely correlated with the prognosis of patients. Knockdown of DDR1 suppressed the migration and invasion of breast cancer cells. Additionally, overexpression of DDR1 enhanced the metastatic capacity of cancer cells. Immunoblotting revealed that activation of Src and FAK, which are involved in cancer cell metastasis, were correlated with the expression level of DDR1. Co-immunoprecipitation experiments showed that DDR1 could bind to Src and FAK. Finally, the inhibition of FAK and Src could attenuate DDR1 enhanced migration ability of breast cancer cells. In summary, our study revealed that DDR1 was highly expressed in breast cancer and negatively correlated with the prognosis of breast cancer patients. DDR1 facilitates migration and invasion in breast cancer cells via activation of the Src-FAK signaling. Accordingly, blocking DDR1/Src/FAK axis is a promising therapeutic strategy for breast cancer treatment.