DDR1 promotes migration and invasion of breast cancer by modulating the Src-FAK signaling
DDR1 promotes migration and invasion of breast cancer by modulating the Src-FAK signaling
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DDR1通过调节Src-FAK信号促进乳腺癌的迁移和侵袭
DOI：
10.4149/neo_2022_220316n289
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发表时间：
2022-01-01
期刊：
影响因子：
3
通讯作者：
DU, Linyong
中科院分区：
文献类型：
--
作者：
Han, Qing;Xiao, Fei;DU, Linyong
乳腺癌是女性中最常见的确诊癌症，导致15%的患者死亡。乳腺癌细胞的转移是导致患者死亡的主要原因。多项研究表明，盘状结构域受体1(DDR1)在乳腺癌中高表达，并可影响肿瘤细胞的行为。然而，DDR1在乳腺癌转移中的具体作用仍不清楚。在这项研究中，我们发现DDR1在乳腺癌中显著增加，并与患者的预后呈负相关。DDR1基因敲除抑制了乳腺癌细胞的迁移和侵袭。此外，DDR1的过表达增强了癌细胞的转移能力。免疫印迹显示参与癌细胞转移的Src和FAK的激活与DDR1的表达水平相关。免疫共沉淀实验表明，DDR1能与Src和FAK结合。最后，抑制FAK和Src可以减弱DDR1增强的乳腺癌细胞的迁移能力。综上所述，我们的研究表明，DDR1在乳腺癌中高表达，并与乳腺癌患者的预后呈负相关。DDR1通过激活Src-FAK信号通路促进乳腺癌细胞的迁移和侵袭。因此，阻断DDR1/Src/FAK轴是乳腺癌治疗的一种有前景的治疗策略。
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.