Related Experiment Video
Updated: Apr 14, 2026
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
NANOG signaling promotes metastatic capability of immunoedited tumor cells
Hyo-Jung Lee1, Kyung Hee Noh, Young-Ho Lee
1Laboratory of Infection and Immunology, Graduate School of Medicine, Korea University, Seoul, Korea.
Abstract:
Metastatic recurrence after cancer treatments with radiation, cancer drugs, or even immunotherapeutic agents (cytokine, antibody, lymphocyte etc.) is often intractable and fatal for cancer patients. Therefore, molecular understanding of metastatic recurrence is necessary. Recently, these recurrent and metastatic tumor cells with resistance to cancer drugs have been reported to possess stem-like attributes and epithelial-mesenchymal transition (EMT) phenotype. Previously, we also found that antigen-specific cytotoxic T lymphocyte (CTL)-mediated immunotherapy conferred tumor cells with immune-resistant and stem-like phenotypes by hyper-activating NANOG/TCL1/AKT signaling axis. In this study, we report that these immunoedited cells have high metastatic capability and phenotypes. These cells exhibit enhanced migration, infiltration, and invasiveness in vitro as well as formation of metastatic lung nodules in vivo. Moreover, they display EMT-like features characterized by increased expression of BMI1 and TWIST1. Importantly, these pleiotropic phenotypes of metastasis through the expression of the EMT-associated molecules were critically dependent on the NANOG/TCL1A/AKT signaling axis, which was also conserved across multiple types of human cancer. Thus, we provide proof of the principle that inhibition of the NANOG axis is an effective strategy to control metastasis of immunoedited cancer, particularly, after CTL-based immunotherapy.
Insights
Cancer recurrence after treatment can lead to metastasis. This study shows that targeting the NANOG signaling axis can control metastasis in immunoedited cancers, especially after T-cell immunotherapy.
Area of Science:
- Oncology
- Immunology
- Cancer Metastasis Research
Background:
- Metastatic recurrence post-cancer treatment is a significant challenge, often linked to drug resistance, stem-like traits, and epithelial-mesenchymal transition (EMT).
- Previous research indicated that cytotoxic T lymphocyte (CTL)-mediated immunotherapy can induce immune-resistant, stem-like phenotypes via NANOG/TCL1/AKT signaling activation.
Purpose of the Study:
- To investigate the metastatic potential of immunoedited cancer cells.
- To elucidate the molecular mechanisms driving metastasis in these cells.
- To validate NANOG signaling axis inhibition as a therapeutic strategy against cancer metastasis.
Main Methods:
- In vitro assays assessing cell migration, infiltration, and invasiveness.
- In vivo studies involving the formation of lung metastatic nodules.
- Analysis of EMT markers (BMI1, TWIST1) and signaling pathway activation (NANOG/TCL1A/AKT).
Main Results:
- Immunoedited cancer cells demonstrated heightened metastatic capabilities, including enhanced migration and invasiveness.
- These cells exhibited EMT-like features with increased BMI1 and TWIST1 expression.
- Metastatic phenotypes were critically dependent on the NANOG/TCL1A/AKT signaling axis, a conserved pathway across human cancers.
Conclusions:
- Immunoedited cancer cells possess high metastatic potential driven by EMT-like phenotypes.
- The NANOG/TCL1A/AKT signaling axis is crucial for mediating these metastatic phenotypes.
- Inhibiting the NANOG axis presents a viable strategy to control metastasis in immunoedited cancers, particularly following CTL-based immunotherapy.
Related Concept Videos
02:17The Tumor Microenvironment
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...