Sequential Treatment with Activin and Hepatocyte Growth Factor Induces FOXM1 to Promote Colorectal Cancer Liver Metastasis

作者全名："Peng, Hong; Ye, Ting; Deng, Lei; Yang, Xiaofang; Jiang, Zheng; Guo, Jinjun"

作者地址："[Peng, Hong; Guo, Jinjun] Chongqing Med Univ, Bishan Hosp Chongqing, Bishan Hosp, Chongqing, Peoples R China; [Ye, Ting; Deng, Lei; Yang, Xiaofang; Guo, Jinjun] Chongqing Univ, Cent Hosp, Chongqing Emergency Med Ctr, Sch Med, Chongqing, Peoples R China; [Jiang, Zheng] Chongqing Med Univ, Dept Gastroenterol, Affiliated Hosp 1, Chongqing, Peoples R China"

通信作者："Guo, JJ (通讯作者)，Chongqing Med Univ, Bishan Hosp Chongqing, Bishan Hosp, Chongqing, Peoples R China.; Guo, JJ (通讯作者)，Chongqing Univ, Cent Hosp, Chongqing Emergency Med Ctr, Sch Med, Chongqing, Peoples R China."

来源：CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000905426400001

JCR分区：Q3

影响因子：2.7

年份：2022

卷号：2022

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Background. 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. Methods. 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. Results. 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 CXCR4. Additionally, CXCR4 regulated AFP expression through the NF-kappa B pathway. Conclusions. 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."

基金机构："Natural Science Foundation of Chongqing, China; [cstc2018jcyjAX0006]; [cstc2021jcyj-msxmX0957]"

基金资助正文："AcknowledgmentsThis work was supported by Natural Science Foundation of Chongqing, China (Grant no. cstc2018jcyjAX0006 to Jinjun Guo, cstc2021jcyj-msxmX0957 to Lei Deng)."