Retinoic acid metabolism in cancer: potential feasibility of retinoic acid metabolism blocking therapy
Retinoic acid metabolism in cancer: potential feasibility of retinoic acid metabolism blocking therapy
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癌症中的视黄酸代谢：视黄酸代谢阻断疗法的潜在可行性
DOI：
10.1007/s00795-022-00345-6
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发表时间：
2023
影响因子：
1.8
通讯作者：
Magara Kazufumi
中科院分区：
文献类型：
--
作者：
Osanai Makoto;Takasawa Akira;Takasawa Kumi;Kyuno Daisuke;Ono Yusuke;Magara Kazufumi
视黄酸（RA）是维生素A的活性代谢物，维生素A是参与多种细胞类型中的细胞命运决定（如分化、增殖和凋亡）的必需信号分子。累积的数据表明，RA代谢酶CYP26 A1、B1和C1（分别为细胞色素P450家族26 A1、B1和C1）的表达通过将RA转化为快速排泄的衍生物来限制RA进入转录机制，从而保护细胞和组织免受RA暴露。CYP26酶在限制营养维生素A波动的后果方面发挥相似但独立的作用。近年来，我们发现CYP26A1表达引起的RA缺失促进了多种组织来源的肿瘤细胞的恶性行为，暗示CYP26A1是一个候选癌基因。我们还表明，CYP26酶的表达水平在各种类型的癌症中升高。我们提供了CYP26酶的致癌和细胞存活特性的证据，表明这些分子是表达CYP26的恶性肿瘤的可能治疗靶点。
Retinoic acid (RA) is an active metabolite of vitamin A, which is an essential signaling molecule involved in cell fate decisions, such as differentiation, proliferation, and apoptosis, in a wide variety of cell types. Accumulated data have demonstrated that expression of RA-metabolizing enzymes, CYP26A1, B1, and C1 (cytochrome P450, family 26A1, B1, and C1, respectively), protects cells and tissues from exposure to RA through restriction of RA access to transcriptional machinery by converting RA to rapidly excreted derivatives. CYP26 enzymes play similar but separate roles in limiting the consequences of fluctuations in nutritional vitamin A. Recently, we found that RA depletion caused by expression of CYP26A1 promotes malignant behaviors of tumor cells derived from various tissues, implicatingCYP26A1as a candidate oncogene. We also showed that the expression levels of CYP26 enzymes are elevated in various types of cancer. We have provided evidence for oncogenic and cell survival properties of CYP26 enzymes, indicating that these molecules are possible therapeutic targets for CYP26-expressing malignancies.