Wnt and BMP signaling enhance melanocyte regeneration and suppress melanoma cell migration

Abstract

ABSTRACTTissue regeneration and cancer share remarkable features including activation of cell proliferation and migration. Yet, tumors considerably differ from the regenerating tissue with respect to abnormal proliferation, invasive growth and metastasis. Thus, it is likely that cancer resembles early stages of regeneration with increased proliferation, but separates from the later stages with reduced proliferation and enhanced differentiation. Here, by exploiting the zebrafish melanocytes that can efficiently regenerate and be induced to undergo malignant melanoma, we unravel the transcriptome profiles of the regenerating melanocytes during early and late regeneration, and the melanocytic nevi and malignant melanoma. Our global comparison of the gene expression profiles of melanocyte regeneration and nevi/melanoma uncovers opposite regulation of Wnt and BMP signaling pathways between regeneration and cancer. Functional inhibition of canonical Wnt or BMP pathways during melanocyte regeneration impeded the regenerative capacity of the melanocytes. In contrast, activation of either pathway significantly promoted melanocyte regeneration and potently suppressed migration of human melanoma cells. Therefore, mechanisms of regeneration can be exploited to correct dysregulated molecular pathways and malignant transformation in cancer.