Abstract 4934: DCBLD2 mediated cisplatin-induced epithelial-to-mesenchymal transition and metastasis in non-small cell lung cancer

Abstract In clinical practice, we observed that many patients with solid tumors were diagnosed with early metastasis after chemotherapy, consistent with a large number of preclinical and clinical repots. However, the mechanism how chemotherapy induced tumor metastasis was seldomly reported. In this work, we found that cisplatin promoted epithelial-to-mesenchymal transition (EMT), cell motility and metastasis in non-small cell lung cancer (NSCLC). Moreover, we validated DCBLD2 was a key mediator in cisplatin-induced metastasis in NSCLC through an in vivo, genome-scale CRISPR/Cas9 activation screening. DCBLD2 was abnormally high-expressed in patients with NSCLC, in accordance with the analysis of TCGA database. The expression level of DCBLD2 was negatively correlated with the prognosis of NSCLC patients. Mechanically, DCBLD2 promoted EMT, cell migration in NSCLC cells and metastasis in a mouse xenograft models by binding to cytoskeletal proteins. In addition, we found that cisplatin played an essential role in promoting DCBLD2 expression. The ERK signaling pathway could be activated by cisplatin with phosphorylated, leading to the transcription factor FOS binding to the promoter region of DCBLD2, upregulating the expression of DCBLD2. In conclude, DCBLD2 was a contextual determinant of chemotherapy and metastatic in NSCLC and a potential target for anti-metastasis drugs. Citation Format: Xiaosu Chen, Yajing Lv, Chongbiao Huang, Rong Xiang. DCBLD2 mediated cisplatin-induced epithelial-to-mesenchymal transition and metastasis in non-small cell lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4934.