FAM172A inhibits EMT in pancreatic cancer via ERK-MAPK signaling.

Ying Chen,Di Shen,Hongkui Wu,Lepeng Xu,Peihui Liu,Daguang Shen,He Sun,Han Liu,Jian Wang

doi:10.1242/bio.048462

Abstract

ABSTRACTFAM172A, 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 (P=0.015), T stage (P=0.006), lymph node metastasis (P=0.028) and the worst prognosis of PC patients (P=0.004). Meanwhile, a positive relationship between FAM172A and E-cadherin (E-cad) (r=0.381, P=0.002) was observed in clinical samples, which contributed to the better prognosis of PC patients (P=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.

Highlights

Pancreatic cancer (PC), as a deadly malignancy, ranks as the fourth leading cancer-related cause of death in Europe (Rawla et al, 2019)
PC tissues with Family with sequence similarity 172 member A (FAM172A) positive expression was associated with E-cad normal expression (Fig. 1B), and vice versa (Fig. 1C)
FAM172A was positively associated with TNM stage, CEA and CA19-9, lymph node involvement and poor prognosis in colorectal cancer (Liu et al, 2017a,b). It indicates that FAM172A exhibits different functions based on different cancer types

Summary

Introduction

Pancreatic cancer (PC), as a deadly malignancy, ranks as the fourth leading cancer-related cause of death in Europe (Rawla et al, 2019). It is ranked as the top first incidence, and second agestandardized cause of mortality in Chinese males (Chen et al, 2016). The poor prognosis for PC patients is mainly due to its aggressive biological behavior, which is boosted by epithelial-tomesenchymal transition (EMT). EMT, as one of the most distinctive and critical features in cancer (Gaianigo et al, 2017), promotes the loss of epithelial character and the gain of invasive mesenchymal properties, and contributes to the highly malignant phenotype in PC (Wang et al, 2017).

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Conclusion