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

Peng, Hong; Ye, Ting; Deng, Lei; Yang, Xiaofang; Jiang, Zheng; Guo, Jinsong

doi:10.1155/2022/8996203

Cited by 2 publications

(2 citation statements)

References 38 publications

(51 reference statements)

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“… 17 In our previous study, we found that activin alone increased the messenger RNA and protein expression of FOXM1 through SMAD family member 2. 18 HGF alone enhanced the phosphorylation of FOXM1, without altering the total protein level of FOXM1. 18 Since activin and HGF have a capacity of promoting an aggressive phenotype in colorectal cancer cells, 18 - 20 we hypothesized that activin and HGF treatment might exert a positive effect on colorectal cancer stemness through FOXM1.…”

Section: Introductionmentioning

confidence: 85%

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

Peng

Deng

et al. 2023

Gut and Liver

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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.

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Section: Introductionmentioning

confidence: 85%

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

Peng

Deng

et al. 2023

Gut and Liver

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“…Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) are some examples of molecules that can be elevated in the serum of CRC with liver metastasis [49,50].…”

Section: Serum Markers/liquid Biopsymentioning

confidence: 99%

Colorectal Cancer Liver Metastasis—State-of-the-Art and Future Perspectives

Ruivo,

Oliveira,

Silva-Vaz

et al. 2023

Gastrointestinal Disorders

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The current management of colorectal cancer liver metastasis (CRCLM) patients involves a multidisciplinary approach, with surgical resection remaining the primary curative option. The advances in liver surgery have improved outcomes, enabling more patients to undergo surgery successfully. In addition, the development of imaging software has improved the preoperative planning and patient selection for surgery and other interventions. Systemic therapies, such as targeted therapies and immunotherapies, have enhanced the chances of complete resection. Targeted agents, in combination with chemotherapy, have shown efficacy in downstaging tumors and increasing resectability. The algorithm approach for these patients continues to evolve, driven by a deeper understanding of the underlying biology. Personalized medicine, guided by molecular profiling and the potential of liquid biopsies in this field, may lead to more tailored treatment strategies. A greater understanding of the immune microenvironment in CRLM may unlock the potential for immune checkpoint inhibitors and novel immunotherapies to become more prominent in the treatment landscape. This review explores the current state-of-the-art treatment of CRCLM and discusses promising future perspectives.

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

Cited by 2 publications

References 38 publications

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

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

Colorectal Cancer Liver Metastasis—State-of-the-Art and Future Perspectives

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