肝母细胞瘤（HB）是最常见的儿童肝脏恶性肿瘤。尽管 HB 治疗取得了进展，但研究 HB 病理机制以优化分层和治疗仍然是改善高危患者预后的焦点。在这里，我们旨在探讨这些机制对 HB 的影响。对 17 名诊断为 HB 的患者的肝脏样本和两个正常肝脏样本进行了一项观察性研究。体外实验是在用 FAK 抑制剂 TAE226 处理的 Huh6 人 HB 细胞系上进行的。我们的结果强调，与正常肝脏相比，HB 肝脏中 FAK 的 mRNA 和蛋白表达显着上调。总 FAK 和 Tyr397 磷酸化 FAK (pTyr397FAK) 蛋白表达的增加与组蛋白 H3 甲基化和乙酰化的一些表观遗传调节因子的表达显着相关。值得注意的是，pTyr397FAK、N-甲基转移酶 (EZH2) 的表达和 H3K27 残基的三甲基化与肿瘤大小和甲胎蛋白 (AFP) 水平相关。最后，TAE226 导致 pTyr397FAK、表观遗传调节因子、AFP、EPCAM、OCT4 和 SOX2 显着减少，与 HB 细胞的抗增殖和促凋亡作用相关。我们的结果表明 FAK 在 HB 中的作用需要进一步研究主要致力于探索其有效的诊断和治疗可翻译性。版权所有 © 2024 Braghini, De Stefanis, Tiano, Castellano, Cicolani, Pezzullo, Tocco, Spada, Alaggio, Alisi 和 Francalanci。

Hepatoblastoma (HB) is the most common pediatric hepatic malignancy. Despite the progress in HB treatment, investigating HB pathomechanisms to optimize stratification and therapies remains a focal point to improve the outcome for high-risk patients.Here, we pointed to explore the impact of these mechanisms in HB. An observational study was performed on liver samples from a cohort of 17 patients with a diagnosis of HB and two normal liver samples. The in vitro experiments were executed on the Huh6 human HB cell line treated with the FAK inhibitor TAE226.Our results highlight a significant up-regulation of mRNA and protein expression of FAK in livers from HB with respect to normal livers. The increased protein expression of total and Tyr397 phosphorylated FAK (pTyr397FAK) was significantly correlated with the expression of some epigenetic regulators of histone H3 methylation and acetylation. Of note, the expression of pTyr397FAK, N-methyltransferase enzyme (EZH2) and tri-methylation of the H3K27 residue correlated with tumor size and alpha-fetoprotein (AFP) levels. Finally, TAE226 caused a significant reduction of pTyr397FAK, epigenetic regulators, AFP, EPCAM, OCT4, and SOX2, in association with anti-proliferative and pro-apoptotic effects on HB cells.Our results suggest a role of FAK in HB that requires further investigations mainly focused on the exploration of its effective diagnostic and therapeutic translatability.Copyright © 2024 Braghini, De Stefanis, Tiano, Castellano, Cicolani, Pezzullo, Tocco, Spada, Alaggio, Alisi and Francalanci.