Activin and Hepatocyte Growth Factor Promotes Colorectal Cancer Stemness and Metastasis through FOXM1/SOX2/CXCR4 Signaling

作者全名："Peng, Hong; Ye, Ting; Deng, Lei; Yang, Xiaofang; Li, Qingling; Tong, Jin; Guo, Jinjun"

作者地址："[Peng, Hong; Guo, Jinjun] Chongqing Med Univ, Bishan Hosp Chongqing, Dept Gastroenterol & Hepatol, Bishan Hosp, Chongqing, Peoples R China; [Ye, Ting; Deng, Lei; Yang, Xiaofang; Tong, Jin] Chongqing Univ, Cent Hosp, Chongqing Emergency Med Ctr, Dept Gastroenterol & Hepatol,Sch Med, Chongqing, Peoples R China; [Li, Qingling] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China"

通信作者："Guo, JJ (通讯作者)，Chongqing Med Univ, Bishan Hosp Chongqing, Dept Gastroenterol & Hepatol, Bishan Hosp, Chongqing, Peoples R China."

来源：GUT AND LIVER

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001033527300001

JCR分区：Q2

影响因子：3.4

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Key Words; Colorectal neoplasms; FOXM1; Neoplasm metastasis; SOX2; Stem cells

摘要："Background/Aims: Cancer stem cells (CSCs) are believed to drive tumor development and metastasis. Activin and hepatocyte growth factor (HGF) are important cytokines with the ability to induce cancer stemness. However, the effect of activin and HGF combination treatment on CSCs is still unclear. Methods: In this study, we sequentially treated colorectal cancer cells with activin and HGF and examined CSC marker expression, self-renewal, tumorigenesis, and metastasis. The roles of forkhead box M1 (FOXM1) and sex-determining region Y-box 2 (SOX2), two stemness-related transcription factors, in activin/HGF-induced aggressive phenotype were explored. Results: Activin and HGF treatment increased the expression of CSC markers and enhanced sphere formation in colorectal cancer cells. The tumorigenic and metastatic capacities of colorectal cancer cells were enhanced upon activin and HGF treatment. Activin and HGF treatment preferentially promoted stemness and metastasis of CD133+ subpopulations sorted from colorectal cancer cells. FOXM1 was upregulated by activin and HGF treatment, and the knockdown of FOXM1 blocked activin/HGF-induced stemness, tumorigenesis, and metastasis of colorectal cancer cells. Similarly, SOX2 was silencing impaired sphere formation of activin/HGF-treated colorectal cancers. Overexpression of SOX2 rescued the stem cell-like phenotype in FOXM1-depleted colorectal cancer cells with activin and HGF treatment. Additionally, the inhibition of FOXM1 via thiostrepton suppressed activin/HGF-induced stemness, tumorigenesis and metastasis. Conclusions: Sequential treatment with activin and HGF promotes colorectal cancer stemness and metastasis through activation of the FOXM1/SOX2 signaling. FOXM1 could be a potential target for the treatment of colorectal cancer metastasis. (Gut Liver, Published online July 17, 2023)"

基金机构："Natural Science Foundation Project of CQ CSTC [cstc2018j- cyjAX0006, cstc2021jcyj-msxmX0957, cst- c2019jcyj-msxmX0752, CSTB2022NSCQ-MSX0137, CSTB2022NSCQ-MSX0105]; Science and Technology Research Project of Chongqing Municipal Education Commission [KJQN202200463]"

基金资助正文："This work was supported by the Natural Science Foundation Project of CQ CSTC (Grant Nos. cstc2018j- cyjAX0006 to J.G., cstc2021jcyj-msxmX0957 to L.D., cst- c2019jcyj-msxmX0752 to J.T., CSTB2022NSCQ-MSX0137 to H.P., CSTB2022NSCQ-MSX0105 to Q.L.) and Science and Technology Research Project of Chongqing Municipal Education Commission (Grant No. KJQN202200463 to H.P.) ."