Department of Intervention Therapy and Vascular Surgery, The Central Hospital of Huludao City, Huludao City, Liaoning Province, 125399 China
Department of Intervention Therapy and Vascular Surgery, The Central Hospital of Huludao City, Huludao City, Liaoning Province, 125399 China.
Biol Open. 2020 Feb 7;9(2):bio048462. doi: 10.1242/bio.048462.
FAM172A, as a newly discovered gene, is little known in cancer development, especially in pancreatic cancer (PC). We investigated the potential role and molecular mechanism of FAM172A in epithelial to mesenchymal transition (EMT) in both human clinical samples and PC cells. FAM172A was downregulated in human PC tissues compared with that in non-cancerous pancreas cells by immunohistochemistry and qRT-PCR. FAM172A expression was negatively associated with tumor size (=0.015), T stage (=0.006), lymph node metastasis (=0.028) and the worst prognosis of PC patients (=0.004). Meanwhile, a positive relationship between FAM172A and E-cadherin (E-cad) (r=0.381, =0.002) was observed in clinical samples, which contributed to the better prognosis of PC patients (=0.014). FAM172A silencing induced EMT in both AsPC-1 and BxPC-3 cells, including inducing the increase of Vimentin, MMP9 and pERK and the decrease of E-cad and β-catenin expression, stimulating EMT-like cell morphology and enhancing cell invasion and migration in PC cells. However, MEK1 inhibitor PD98059 reversed FAM172A silencing-enhanced EMT in PC cells. We conclude that FAM172A inhibits EMT of PC cells via ERK-MAPK signaling.
FAM172A 作为一个新发现的基因，在癌症发展中，尤其是在胰腺癌（PC）中知之甚少。我们研究了 FAM172A 在人临床样本和 PC 细胞中的上皮间质转化（EMT）中的潜在作用和分子机制。免疫组化和 qRT-PCR 结果显示，与非癌胰腺细胞相比，人 PC 组织中 FAM172A 表达下调。FAM172A 的表达与肿瘤大小（=0.015）、T 分期（=0.006）、淋巴结转移（=0.028）和 PC 患者最差预后（=0.004）呈负相关。同时，临床样本中 FAM172A 与 E-钙黏蛋白（E-cad）（r=0.381，=0.002）呈正相关，这有助于 PC 患者的更好预后（=0.014）。FAM172A 沉默在 AsPC-1 和 BxPC-3 细胞中诱导 EMT，包括诱导波形蛋白、MMP9 和 pERK 的增加，以及 E-cad 和 β-连环蛋白表达的减少，刺激 EMT 样细胞形态，并增强 PC 细胞的侵袭和迁移。然而，MEK1 抑制剂 PD98059 逆转了 FAM172A 沉默增强的 EMT。我们得出结论，FAM172A 通过 ERK-MAPK 信号抑制 PC 细胞的 EMT。
