PT  - JOURNAL ARTICLE
AU  - HIPPNER-KUNICKA, MIRIAM
AU  - LASZKIEWICZ, AGNIESZKA
AU  - SKRZYMOWSKA, JOANNA
AU  - BIECEK, PRZEMYSLAW
AU  - DONIZY, PIOTR
AU  - MIAZEK, ARKADIUSZ
TI  - Overexpression of <em>c-MYC</em> Promoter Binding Protein-1 Enhances Proliferation and Glucose Metabolism of Melanoma Cells Lines
AID  - 10.21873/anticanres.16420
DP  - 2023 Jun 01
TA  - Anticancer Research
PG  - 2527--2538
VI  - 43
IP  - 6
4099  - http://ar.iiarjournals.org/content/43/6/2527.short
4100  - http://ar.iiarjournals.org/content/43/6/2527.full
SO  - Anticancer Res2023 Jun 01; 43
AB  - Background/Aim: c-MYC promoter binding protein (MBP-1) is a product of alternatively translated mRNA encoding alpha-enolase (ENO1). In contrast to ENO1, MBP-1 possesses no enzymatic activity but acts as a transcriptional repressor of c-MYC. Ectopic over-expression of MBP-1 in tumor cells was shown to reduce cell proliferation and tumorigenicity, thus making it an attractive target for anticancer strategies. This study aimed to assess the effects of MBP-1 over-expression on human cutaneous melanoma cell lines. Materials and Methods: We overexpressed the full-length MBP-1 or its C-terminal truncated variant (MBP-1ΔC), in two human melanoma cell lines (A375, WM9) and assessed their subcellular localization. qPCR was then used to quantitate c-MYC transcription. Further, 5-ethynyl-2′-deoxyuridine incorporation assay was used to measure cell proliferation and a lactate assay was performed to measure the glycolysis rate of cells in normoxia and hypoxia. Finally, an in vitro wound-healing assay was performed to evaluate cell migration. Results: The overexpressed MBP-1 variants predominantly localized in the cytoplasm and barely decreased c-MYC expression. Unexpectedly, the proliferation rate of MBP-1- transduced cells increased in comparison to controls, as did the rate of glucose metabolism in hypoxia. Furthermore, over-expression of MBP-1, but not MBP-1ΔC, led to a substantial decrease in the cell migration capacity of metastatic WM9 cells but not A375 cells from the primary tumor lesion. Conclusion: Misslocalization of over-expressed MBP-1 in the cytoplasm of two melanoma cell lines resulted in an unexpected tumor promoting activity by increasing cell proliferation and glycolysis rates in hypoxia.