Nodal-induced L1CAM/CXCR4 subpopulation sustains tumor growth and metastasis in colorectal cancer derived organoids

Background: Colorectal cancer (CRC) is currently the third leading cause for cancer-related mortality. Cancer stem cells have been implicated in colorectal tumor growth, but their specific role biology, including metastasis, still uncertain. Methods: Increased expression of L1CAM, CXCR4 and NODAL was identified section patients with CRC patients-derived-organoids (PDOs). The evaluated using quantitative real-time PCR, western blotting, immunofluorescence, immunohistochemistry flow cytometry. effects on proliferation, migration, invasion, colony-formation ability, metastasis chemoresistance were investigated both vitro vivo. Results: We found that human tissue contains defined by L1CAMhigh/CXCR4high activated Nodal hypoxic microenvironment. This population tumorigenic, highly resistant to standard chemotherapy, determines metastatic phenotype individual tumor. Depletion drastically reduces tumorigenic potential tumors. Conclusion: In conclusion, we demonstrated a subpopulation migrating essential progression. Together, these findings suggest strategies aimed at modulating signaling could important clinical applications inhibit cancer-derived metastasis.