TY - JOUR AU - Zhang Le-le AU - Lu Jun AU - Liu Rui-qi AU - Hu Min-juan AU - Zhao Yi-ming AU - Tan Sheng AU - Wang Shu-yuan AU - Zhang Bo AU - Nie Wei AU - Dong Yu AU - Zhong Hua AU - Zhang Wei AU - Zhao Xiao-dong AU - Han Bao-hui PY - 2020 TI - Chromatin accessibility analysis reveals that TFAP2A promotes angiogenesis in acquired resistance to anlotinib in lung cancer cells JF - Acta Pharmacologica Sinica; Vol 41, No 10 (October 2020): Acta Pharmacologica Sinica Y2 - 2020 KW - N2 - Anlotinib, a multitarget tyrosine kinase inhibitor, is effective as a third-line treatment against non-small cell lung cancer (NSCLC). However, acquired resistance occurs during its administration. To understand the molecular mechanisms of anlotinib resistance, we characterized chromatin accessibility in both the parental and anlotinib-resistant lung cancer cell line NCI-H1975 through ATAC-seq. Compared with the parental cells, we identified 2666 genomic regions with greater accessibility in anlotinib-resistant cells, in which angiogenesis-related processes and the motifs of 21 transcription factors were enriched. Among these transcription factors, TFAP2A was upregulated. TFAP2A knockdown robustly diminished tumor-induced angiogenesis and partially rescued the anti-angiogenic activity of anlotinib. Furthermore, transcriptome analysis indicated that 2280 genes were downregulated in anlotinib-resistant cells with TFAP2A knocked down, among which the PDGFR, TGF-β, and VEGFR signaling pathways were enriched. Meanwhile, we demonstrated that TFAP2A binds to accessible sites within BMP4 and HSPG2 . Collectively, this study suggests that TFAP2A accelerates anlotinib resistance by promoting tumor-induced angiogenesis. UR - http://www.chinaphar.com/article/view/10214