Departamento de Bioquímica UAM, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, 28029 Madrid, Spain.
Instituto de Investigación Sanitaria del Hospital Universitario La Paz-IdiPAZ, 28029 Madrid, Spain.
Molecules. 2023 May 30;28(11):4433. doi: 10.3390/molecules28114433.
Lysyl oxidase-like 2 (LOXL2) was initially described as an extracellular enzyme involved in extracellular matrix remodeling. Nevertheless, numerous recent reports have implicated intracellular LOXL2 in a wide variety of processes that impact on gene transcription, development, differentiation, proliferation, migration, cell adhesion, and angiogenesis, suggesting multiple different functions for this protein. In addition, increasing knowledge about LOXL2 points to a role in several types of human cancer. Moreover, LOXL2 is able to induce the epithelial-to-mesenchymal transition (EMT) process-the first step in the metastatic cascade. To uncover the underlying mechanisms of the great variety of functions of intracellular LOXL2, we carried out an analysis of LOXL2's nuclear interactome. This study reveals the interaction of LOXL2 with numerous RNA-binding proteins (RBPs) involved in several aspects of RNA metabolism. Gene expression profile analysis of cells silenced for LOXL2, combined with in silico identification of RBPs' targets, points to six RBPs as candidates to be substrates of LOXL2's action, and that deserve a more mechanistic analysis in the future. The results presented here allow us to hypothesize novel LOXL2 functions that might help to comprehend its multifaceted role in the tumorigenic process.
赖氨酰氧化酶样蛋白 2（LOXL2）最初被描述为一种参与细胞外基质重塑的细胞外酶。然而，最近的许多报告表明，细胞内 LOXL2 参与了广泛的过程，这些过程影响基因转录、发育、分化、增殖、迁移、细胞黏附和血管生成，提示该蛋白具有多种不同的功能。此外，对 LOXL2 的认识不断增加，表明其在几种类型的人类癌症中发挥作用。此外，LOXL2 能够诱导上皮-间充质转化（EMT）过程——转移级联的第一步。为了揭示细胞内 LOXL2 多种功能的潜在机制，我们对 LOXL2 的核相互作用组进行了分析。这项研究揭示了 LOXL2 与参与 RNA 代谢多个方面的许多 RNA 结合蛋白（RBP）的相互作用。对 LOXL2 沉默的细胞进行基因表达谱分析，并结合 RBP 靶标的计算鉴定，指出有 6 个 RBP 可能是 LOXL2 作用的底物，值得在未来进行更深入的机制分析。这里呈现的结果使我们能够假设 LOXL2 的新功能，这可能有助于理解其在肿瘤发生过程中的多方面作用。
