DCLK1 Plays a Metastatic-Promoting Role in Human Breast Cancer Cells

作者：Heshu Liu, Tao Wen, Ying Zhou, Xiaona Fan, Tan Du, Tianbo Gao, Lina Li, Jian Liu, Lei Yang, Jiannan Yao, Yang Ge, Guangyu An · 发表于：BioMed Research International · 年份：2019 · DOI：10.1155/2019/1061979 · 被引用次数：43 · 研究领域：Cancer Cells and Metastasis、Hippo pathway signaling and YAP/TAZ、Caveolin-1 and cellular processes

BACKGROUND: Doublecortin-like kinase 1 (DCLK1) has been universally identified as a cancer stem cell (CSC) marker and is found to be overexpressed in many types of cancers including breast cancer. However, there is little data regarding the functional role of DCLK1 in breast cancer metastasis. In the present study, we sought to investigate whether and how DCLK1 plays a metastatic-promoting role in human breast cancer cells. METHODS: We used Crispr/Cas9 technology to knock out DCLK1 in breast cancer cell line BT474, which basically possesses DCLK1 at a higher level, and stably overexpressed DCLK1 in another breast cancer cell line, T47D, that basically expresses DCLK1 at a lower level. We further analyzed the alterations of metastatic characteristics and the underlying mechanisms in these cells. RESULTS: It was shown that, compared with the corresponding control cells, DCLK1 overexpression led to an increase in metastatic behaviors including enhanced migration and invasion of T47D cells. By contrast, forced depletion of DCLK1 drastically inhibited these metastatic characteristics in BT474 cells. Mechanistically, the epithelial-mesenchymal transition (EMT) program, which is critical for cancer metastasis, was prominently activated in DCLK1-overexpressing cancer cells, evidenced by a decrease in an epithelial marker ZO-1 and an enhancement in several mesenchymal markers including ZEB1 and Vimentin. In addition, DCLK1 overexpression induced the ERK MAPK pathway, which resultantly...