Runx3 Induces a Cell Shape Change and Suppresses Migration and Metastasis of Melanoma Cells by Altering a Transcriptional Profile

Runt-related transcription factor-3 (Runx3) is a tumor suppressor, and its contribution to melanoma progression remains unclear. We previously demonstrated that Runx3 re-expression in B16-F10 melanoma cells changed their shape and attenuated their migration. In this study, we found that Runx3 re-expression in B16-F10 cells also suppressed their pulmonary metastasis. We performed microarray analysis and uncovered an altered transcriptional profile underlying the cell shape change and the suppression of migration and metastasis. This altered transcriptional profile was rich in Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG) annotations relevant to adhesion and the actin cytoskeleton and included differentially expressed genes for some major extracellular matrix (ECM) proteins as well as genes that were inversely associated with the increase in the metastatic potential of B16-F10 cells compared to B16-F0 melanoma cells. Further, we found that this altered transcriptional profile could have prognostic value, as evidenced by myelin and lymphocyte protein (MAL) and vilin-like (VILL). Finally, Mal gene expression was correlated with metastatic potential among the cells and was targeted by histone deacetylase (HDAC) inhibitors in B16-F10 cells, and the knockdown of Mal gene expression in B16-F0 cells changed their shape and enhanced the migratory and invasive traits of their metastasis. Our study suggests that self-entrapping of metastatic Runx3-negative melanoma cells via adhesion and the actin cytoskeleton could be a powerful therapeutic strategy.

Automated summary

Runx3 re-expression in B16-F10 melanoma cells alters their shape, attenuates migration, and suppresses pulmonary metastasis, revealing a potential therapeutic strategy for metastatic melanoma. Microarray analysis uncovers an altered transcriptional profile rich in annotations related to adhesion, actin cytoskeleton, and extracellular matrix proteins, with prognostic value demonstrated by MAL and VILL genes. Knockdown of MAL gene expression in B16-F0 cells enhances migratory and invasive traits, highlighting the significance of adhesion and actin cytoskeleton in melanoma metastasis.