Bishan Hospital of Chongqing, Bishan Hospital of Chongqing Medical University, Chongqing, China.
Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, China.
Can J Gastroenterol Hepatol. 2022 Dec 23;2022:8996203. doi: 10.1155/2022/8996203. eCollection 2022.
Cancer stem cells (CSCs) are involved in liver metastasis in colorectal cancer (CRC). Activin and hepatocyte growth factor (HGF) are important regulators of stem cell properties. This study was performed to explore the effect of activin and HGF on CRC invasion and metastasis. The key genes involved in the action of activin and HGF in CRC were identified.
HCT116 CRC cells were sequentially treated with activin and HGF and examined for migration and invasion in vitro and liver metastasis in vivo. RNA sequencing was performed to identify differentially expressed genes in response to activin and HGF.
Sequential treatment with activin and HGF-enhanced CRC cell migration, invasion, and metastasis. CXCR4 and AFP expressions were increased by activin and HGF treatment. Knockdown of FOXM1 blocked liver metastasis from HCT116 cells pretreated with activin and HGF and suppressed CXCR4 and AFP expression. Activin alone increased the mRNA and protein expression of FOXM1. In contrast, HGF alone enhanced the phosphorylation of FOXM1, without altering the total protein level of FOXM1. SMAD2 was required for activin-mediated FOXM1 induction. FOXM1 transactivated CXCR4 by directly binding to the promoter of . Additionally, CXCR4 regulated AFP expression through the NF-B pathway.
Sequential treatment with activin and HGF accelerates CRC invasion and liver metastasis, which involves the upregulation and activation of FOXM1 and induction of CXCR4 and AFP.
癌症干细胞（CSCs）参与结直肠癌（CRC）的肝转移。激活素和肝细胞生长因子（HGF）是干细胞特性的重要调节剂。本研究旨在探讨激活素和 HGF 对 CRC 侵袭和转移的影响。确定了激活素和 HGF 在 CRC 中作用的关键基因。
HCT116 CRC 细胞依次用激活素和 HGF 处理，体外检测迁移和侵袭，体内检测肝转移。进行 RNA 测序以鉴定对激活素和 HGF 有反应的差异表达基因。
激活素和 HGF 的序贯处理增强了 CRC 细胞的迁移、侵袭和转移。CXCR4 和 AFP 的表达被激活素和 HGF 处理上调。FOXM1 的敲低阻止了经激活素和 HGF 预处理的 HCT116 细胞的肝转移，并抑制了 CXCR4 和 AFP 的表达。激活素单独增加了 FOXM1 的 mRNA 和蛋白表达。相比之下，HGF 单独增强了 FOXM1 的磷酸化，而不改变 FOXM1 的总蛋白水平。SMAD2 是激活素介导的 FOXM1 诱导所必需的。FOXM1 通过直接结合 CXCR4 的启动子来转录激活 CXCR4。此外，CXCR4 通过 NF-B 通路调节 AFP 的表达。
激活素和 HGF 的序贯处理加速了 CRC 的侵袭和肝转移，涉及 FOXM1 的上调和激活，以及 CXCR4 和 AFP 的诱导。
