Zebrafish Xenografts Reveal a Context-dependent Role of PFKFB4 in Melanoma Cell

Cutaneous melanoma is a highly metastatic cancer in which tumor cell plasticity drives transitions between proliferative and invasive states. The glycolytic regulator PFKFB4 has been implicated in cancer cell motility, but its role in melanoma progression in vivo remains unclear. Using zebrafish larval xenografts, we found that PFKFB4 depletion reduced invasion in MeWo cells without affecting tumor growth, whereas in A375P cells it decreased tumor growth but had no effect on invasion or metastasis. In MeWo, PFKFB4 loss was associated with reduced SNAIL2 expression, while no effect on EMT transcription factors was observed in A375P cells. Rescue experiments indicated that PFKFB4 and SNAIL2 acted independently in regulating Mewo migration in vitro . These findings identify PFKFB4 as a context-dependent regulator of melanoma progression.