Oleic acid‐bound FABP7 drives glioma cell proliferation through regulation of nuclear lipid droplet formation
Oleic acid‐bound FABP7 drives glioma cell proliferation through regulation of nuclear lipid droplet formation
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DOI：
10.1111/febs.16672
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发表时间：
2022-11
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影响因子：
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通讯作者：
Banlanjo Umaru;Yoshiteru Kagawa;Yuki Ohsaki;Yijun Pan;Chuck T. Chen;Daniel K. Chen;T. Abe;S. K. Shil;Hirofumi Miyazaki;Shuhei Kobayashi;M. Maekawa;Yui Yamamoto;Tunyanat Wannakul;Shuhan Yang;R. Bazinet;Y. Owada
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作者：
Banlanjo Umaru;Yoshiteru Kagawa;Yuki Ohsaki;Yijun Pan;Chuck T. Chen;Daniel K. Chen;T. Abe;S. K. Shil;Hirofumi Miyazaki;Shuhei Kobayashi;M. Maekawa;Yui Yamamoto;Tunyanat Wannakul;Shuhan Yang;R. Bazinet;Y. Owada
脂肪酸结合蛋白7(FABP7)是参与调节细胞内FA代谢的脂肪酸伴侣蛋白之一，在胶质母细胞瘤中高表达，其表达与患者预后下降有关。此前，我们证明了FABP7需要其结合伙伴才能发挥其功能，并且FABP7 FA结合位点的突变会影响肿瘤生物学。在这里，我们探索了FABP7功能的FA配体结合在肿瘤增殖中的作用，并探讨了FABP7及其配体相互作用在肿瘤生物学中的作用机制。我们发现在几种FA处理中，油酸(OA)促进了FABP7表达细胞的增殖。反过来，OA增加了FABP7的核定位，FABP7-OA复合体在细胞核内的积聚导致了核脂滴(NLD)的形成，以及NLD与早幼粒细胞白血病(PML)核体共存的增加。此外，OA通过组蛋白乙酰化增加FABP7表达细胞中增殖相关基因的mRNA水平。有趣的是，这些由OA增强的功能在FABP7基因敲除细胞和突变的FABP7过表达细胞中被取消。因此，我们的研究结果表明，FABP7-OA细胞内相互作用可能调节NLD的形成和表观遗传状态，从而增强增殖调节基因的转录，最终推动肿瘤细胞的增殖。
Fatty acid‐binding protein 7 (FABP7), one of the fatty acid (FA) chaperones involved in the modulation of intracellular FA metabolism, is highly expressed in glioblastoma, and its expression is associated with decreased patients' prognosis. Previously, we demonstrated that FABP7 requires its binding partner to exert its function and that a mutation in the FA‐binding site of FABP7 affects tumour biology. Here, we explored the role of FA ligand binding for FABP7 function in tumour proliferation and examined the mechanism of FABP7 and ligand interaction in tumour biology. We discovered that among several FA treatment, oleic acid (OA) boosted cell proliferation of FABP7‐expressing cells. In turn, OA increased FABP7 nuclear localization, and the accumulation of FABP7–OA complex in the nucleus induced the formation of nuclear lipid droplet (nLD), as well as an increase in colocalization of nLD with promyelocytic leukaemia (PML) nuclear bodies. Furthermore, OA increased mRNA levels of proliferation‐related genes in FABP7‐expressing cells through histone acetylation. Interestingly, these OA‐boosted functions were abrogated in FABP7‐knockout cells and mutant FABP7‐overexpressing cells. Thus, our findings suggest that FABP7–OA intracellular interaction may modulate nLD formation and the epigenetic status thereby enhancing transcription of proliferation‐regulating genes, ultimately driving tumour cell proliferation.