Ligand Bound Fatty Acid Binding Protein 7 (FABP7) Drives Melanoma Cell Proliferation Via Modulation of Wnt/β-Catenin Signaling
Ligand Bound Fatty Acid Binding Protein 7 (FABP7) Drives Melanoma Cell Proliferation Via Modulation of Wnt/β-Catenin Signaling
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DOI：
10.1007/s11095-021-03009-9
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发表时间：
2021-03-01
影响因子：
3.7
通讯作者：
Owada, Yuji
中科院分区：
文献类型：
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作者：
Umaru, Banlanjo Abdulaziz;Kagawa, Yoshiteru;Owada, Yuji
目的脂肪酸结合蛋白7（FABP 7）参与细胞内脂质动力学，在黑色素瘤中高表达，与患者生存率降低相关。一些研究将FABP 7置于黑色素瘤细胞增殖的中心。然而，其内在机制尚未得到很好的解释。本研究检测了FABP 7对Wnt/β-连环蛋白信号传导的影响，该信号传导增强黑素瘤细胞中的增殖。方法使用具有FABP 7沉默的Slonel 23细胞和用野生型FABP 7（FABP 7 wt）和突变型FABP 7（FABP 7 mut）过表达的Mel 2细胞。细胞增殖和迁移分别通过增殖和伤口愈合试验进行分析。Wnt/β-连环蛋白信号传导的转录激活通过荧光素酶报告基因测定来测量。FABP 7特异性抑制剂MF 6对Skinel 23细胞增殖、迁移和Wnt/beta-catenin信号转导的影响进行了检测。类似地，FABP 7 wt在Mel 2细胞中的过表达增强了这些作用，但FABP 7 mut消除了这些作用。MF 6对FABP 7功能的药理学抑制抑制FABP 7调节的黑素瘤细胞增殖。结论这些结果表明FABP 7与其配体之间的相互作用在黑素瘤增殖调节中的重要性，以及FABP 7靶向治疗黑素瘤的有益意义。
Purpose Fatty acid-binding protein 7 (FABP7) involved in intracellular lipid dynamics, is highly expressed in melanomas and associated with decreased patient survival. Several studies put FABP7 at the center of melanoma cell proliferation. However, the underlying mechanisms are not well deciphered. This study examines the effects of FABP7 on Wnt/beta-catenin signaling that enhances proliferation in melanoma cells.Methods Slonel23 cells with FABP7 silencing and Mel2 cells overexpressed with wild-type FABP7 (FABP7wt) and mutated FABP7 (FABP7mut) were used. Cell proliferation and migration were analyzed by proliferation and wound-healing assay, respectively. Transcriptional activation of the Wnt/beta-catenin signaling was measured by luciferase reporter assay. The effects of a specific FABP7 inhibitor, MF6, on proliferation, migration, and modulation of the Wnt/beta-catenin signaling were examined.Results FABP7 siRNA knockdown in Skinel23 decreased proliferation and migration, cyclin D1 expression, as well as Wnt/beta-catenin activity. Similarly, FABP7wt overexpression in Mel2 cells increased these effects, hut FABP7mut abrogated these effects. Pharmacological inhibition of FABP7 function with MF6 suppressed FABP7-regulated proliferation of melanoma cells.Conclusion These results suggest the importance of the interaction between FABP7 and its ligands in melanoma proliferation modulation, and the beneficial implications of therapeutic targeting of FABP7 for melanoma treatment.