The TP53 gene has been widely studied for its roles in cell cycle control, maintaining genome stability, activating repair mechanisms upon DNA damage, and initiating apoptosis should repair mechanisms fail. Thus, it is not surprising that mutations of p53 are the most common genetic alterations found in human cancer. Emerging evidence indicates that dysregulation of lipid metabolism by p53 can have a profound impact not only on cancer cells but also cells of the tumor microenvironment (TME). In particular, intermediates of the sphingolipid and lysophospholipid pathways regulate many cellular responses common to p53 such as cell survival, migration, DNA damage repair and apoptosis. The majority of these cellular events become dysregulated in cancer as well as cell senescence. In this review, we will provide an account on the seminal contributions of Prof. Lina Obeid, who deciphered the crosstalk between p53 and the sphingolipid pathway particularly in modulating DNA damage repair and apoptosis in non-transformed as well as transformed cells. We will also provide insights on the integrative role of p53 with the lysophosphatidic acid (LPA) signaling pathway in cancer progression and TME regulation.

该TP53基因已被广泛研究，因为它在细胞周期控制、维持基因组稳定性、DNA 损伤时激活修复机制以及在修复机制失败时启动细胞凋亡中的作用。因此，p53 的突变是人类癌症中发现的最常见的基因改变也就不足为奇了。新出现的证据表明，p53 对脂质代谢的失调不仅对癌细胞而且对肿瘤微环境 (TME) 的细胞都有深远的影响。特别是，鞘脂和溶血磷脂通路的中间体调节 p53 常见的许多细胞反应，如细胞存活、迁移、DNA 损伤修复和细胞凋亡。大多数这些细胞事件在癌症和细胞衰老中变得失调。在这篇评论中，我们将介绍教授的开创性贡献。Lina Obeid，他破译了 p53 和鞘脂通路之间的串扰，特别是在调节非转化细胞和转化细胞的 DNA 损伤修复和细胞凋亡方面。我们还将提供有关 p53 与溶血磷脂酸 (LPA) 信号通路在癌症进展和 TME 调节中的整合作用的见解。