Wieczorek-Szukala Katarzyna, Kopczynski Janusz, Kowalska Aldona, Lewinski Andrzej
Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, 93-338 Lodz, Poland.
Department of Pathology, Holy Cross Cancer Center, 25-734 Kielce, Poland.
J Clin Med. 2020 Aug 21;9(9):2701. doi: 10.3390/jcm9092701.
The ability of cancer to metastasize is regulated by various signaling pathways, including transforming growth factor β (TGFβ), also implicated in the upregulation of Snail-1 transcription factor in malignant neoplasms. B-type Raf kinase gene (BRAF), the most common driving mutation in papillary thyroid carcinoma (PTC), induces epithelial to mesenchymal transition (EMT) in thyroid cancer cells through changes in the Snail-1 level, increasing cell migration and invasion. However, little is known about the mechanism of Snail-1 and BRAF relations in humans. Our study included 61 PTC patients with evaluated BRAF mutation status. A total of 18 of those patients had lymph node metastases-of whom 10 were BRAF positive, and 8 negative. Our findings indicate that the expression of Snail-1, but not TGFβ1, correlates with the metastatic phenotype in PTC. This is the first piece of evidence that the upregulation of Snail-1 corresponds with the presence of BRAF mutation and increased expression of Snail-1 in metastatic PTC samples is dependent on BRAF mutation status.
癌症的转移能力受多种信号通路调控，包括转化生长因子β（TGFβ），其也与恶性肿瘤中Snail-1转录因子的上调有关。B型Raf激酶基因（BRAF）是甲状腺乳头状癌（PTC）中最常见的驱动突变，通过改变Snail-1水平诱导甲状腺癌细胞发生上皮-间质转化（EMT），增加细胞迁移和侵袭。然而，关于人类中Snail-1与BRAF关系的机制知之甚少。我们的研究纳入了61例评估了BRAF突变状态的PTC患者。其中共有18例患者发生淋巴结转移，其中10例BRAF阳性，8例阴性。我们的研究结果表明，Snail-1而非TGFβ1的表达与PTC的转移表型相关。这是首个证据表明Snail-1的上调与BRAF突变的存在相对应，且转移性PTC样本中Snail-1表达增加依赖于BRAF突变状态。
