Depletion of GRIM-19 accelerates hepatocellular carcinoma invasion via inducing EMT and loss of contact inhibition

作者：Hao Hongbo; Liu Jun; Liu Guoliang; Guan Dongshi; Yang Yang; Zhang Xiuqing; Cao Xinmin; Liu Qian^*

来源：Journal of Cellular Physiology, 2012, 227(3): 1212-1219.

DOI：10.1002/jcp.24025

Genes associated with retinoid-interferon-induced mortality 19 (GRIM-19) was identified as a tumor suppressor protein associated with apoptosis and growth inhibition. Here, we report that the expression levels of GRIM-19 are significantly attenuated in hepatocellular carcinoma (HCC) patients with deteriorating differentiation states, hepatic capsule invasion and microvascular invasion, suggesting the potential role of GRIM-19 not only at the origin but also in the invasive progression of HCCs. To dissect the possible mechanisms by which GRIM-19 regulates tumor cell invasion, we established the hepatic HL-7702 and HCC Huh-7 cell lines stably depleted of GRIM-19. Results show that downregulation of GRIM-19 induces a morphological transformation resembling epithelialmesenchymal transition (EMT) as well as aberrant expression of epithelial and mesenchymal molecular markers. Additionally, these cells lose contact inhibition, a phenomenon of cessation of cell migration in contact with neighboring cells, as assessed by cell imaging, growth curve and S-phase transition in confluent conditions. Conclusion: Our observations demonstrate a novel mechanistic insight into a critical role of GRIM-19 in HCC invasive potential. J. Cell. Physiol. 227: 12121219, 2012.

• 出版日期2012-3
• 单位山东大学