Kuo Chi-Yu, Hsu Yi-Chiung, Liu Chien-Liang, Li Ying-Syuan, Chang Shao-Chiang, Cheng Shih-Ping
Department of Surgery, MacKay Memorial Hospital, Taipei, Taiwan; Department of Medicine, School of Medicine, MacKay Medical College, New Taipei City, Taiwan.
Department of Biomedical Sciences and Engineering, National Central University, Taoyuan City, Taiwan.
Mol Cell Endocrinol. 2023 Dec 1;578:112062. doi: 10.1016/j.mce.2023.112062. Epub 2023 Sep 4.
The SOX family consists of about 20 transcription factors involved in embryonic development, reprogramming, and cell fate determination. In this study, we demonstrated that SOX4 was significantly upregulated in differentiated thyroid cancer. Immunohistochemical analysis revealed that high SOX4 expression was associated with papillary histology, extrathyroidal extension, lymph node metastasis, and advanced disease stage. Patients whose tumors exhibited high SOX4 expression had a shorter recurrence-free survival, though significance was lost in multivariate Cox regression analysis. SOX4 silencing in thyroid cancer cells slowed cell growth, attenuated clonogenicity, and suppressed anoikis resistance. Additionally, SOX4 knockdown impeded xenograft tumor growth in nude mice. Knockdown of SOX4 expression was accompanied by reduced phosphorylation of AKT and ERK. Furthermore, CRABP2 expression correlated with SOX4 expression, and SOX4 silencing decreased CRABP2 expression and its downstream effectors such as integrin β1 and β4. These results indicate that SOX4 has both prognostic and therapeutic implications in differentiated thyroid cancer, and targeting SOX4 may modulate tumorigenic processes in the thyroid.
SOX家族由大约20种参与胚胎发育、重编程和细胞命运决定的转录因子组成。在本研究中，我们证明SOX4在分化型甲状腺癌中显著上调。免疫组织化学分析显示，SOX4高表达与乳头状组织学、甲状腺外侵犯、淋巴结转移和疾病晚期相关。肿瘤表现出SOX4高表达的患者无复发生存期较短，尽管在多变量Cox回归分析中失去了显著性。甲状腺癌细胞中的SOX4沉默减缓了细胞生长，减弱了克隆形成能力，并抑制了失巢凋亡抗性。此外，SOX4敲低阻碍了裸鼠体内异种移植瘤的生长。SOX4表达的敲低伴随着AKT和ERK磷酸化的减少。此外，CRABP2表达与SOX4表达相关，SOX4沉默降低了CRABP2表达及其下游效应分子如整合素β1和β4。这些结果表明，SOX4在分化型甲状腺癌中具有预后和治疗意义，靶向SOX4可能调节甲状腺的致瘤过程。
