DCBLD2 Affects the Development of Colorectal Cancer via EMT and Angiogenesis and Modulates 5-FU Drug Resistance

作者：Pan Xie, Fuqiang Yuan, Masha Huang, Wei Zhang, Hong‐Hao Zhou, Xi Li, Zhaoqian Liu · 发表于：Frontiers in Cell and Developmental Biology · 年份：2021 · DOI：10.3389/fcell.2021.669285 · 被引用次数：30 · 研究领域：Caveolin-1 and cellular processes、RNA Research and Splicing、Cancer, Hypoxia, and Metabolism

Background: DCBLD2 is highly expressed in various cancers, including colorectal cancer. DCBLD2 overexpression promotes tumor occurrence, development, and metastasis. However, DCBLD2 sensitivity to chemotherapy drugs and its mechanism on tumor development are unknown. Methods: DCBLD2 expression differences in cancer and normal tissues were obtained from GEO and TCGA databases. DCBLD2 influence on prognosis was also compared, and the database analysis results were verified via the analysis of clinical samples. GDSC database was used to analyze the effect of DCBLD2 expression difference on 5-FU drug sensitivity on tumor cells. CCK-8, clone formation, scratch, Transwell invasion and migration assays were used to assess DCBLD2 effects on the proliferation, metastasis, and 5-FU drug sensitivity on HCT116 and Caco-2 colorectal cancer cells. Angiogenesis and Matrigel plug assays were used to study the effect of DCBLD2 on angiogenesis. Q-RCR and Western Blot were used to analyze DCBLD2 impact on the EMT signaling pathway, and TAP-MS assay with Co-IP verification was used to identify the downstream target proteins binding to DCBLD2. Results: Both database and clinical sample validation results showed that the expression of DCBLD2 in colorectal cancer tissues was significantly higher than that in normal tissues, leading to poor prognosis of patients. GDSC database analysis showed that DCBLD2 overexpression caused tumor cell resistance to 5-FU. The results of in vitro and in vivo experim...