Tg737 signaling is required for hypoxia-enhanced invasion and migration of hepatoma cells

Journal of Experimental & Clinical Cancer Research

Kaishan Tao¹  Kefeng Dou¹  Yong He¹  Desheng Wang¹  Ning Zhang¹  Ru Ji¹  Xiao Zhong²  Lijun Tang³  Weihui Liu³  Nan You¹ 

[1] Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China;Department of Urology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400038, PR China;PLA Center of General Surgery; General Hospital of Chengdu Army Region, Chengdu, 610083, China

关键词: Invasion;    Migration;    Hypoxia;    Hepatocellular carcinoma (HCC);    Tg737;   

Others  :  825940
DOI  :  10.1186/1756-9966-31-75

 received in 2012-07-10, accepted in 2012-09-03,  发布年份 2012

【 摘 要 】

Background

Although hypoxia is known to promote hepatoma cell invasion and migration, little is known regarding the molecular mechanisms of this process. Our previous research showed that loss of Tg737 is associated with hepatoma cell invasion and migration; therefore, we hypothesized that the Tg737 signal might be required for hypoxia-enhanced invasion and migration.

Methods

We established in vitro normoxic or hypoxic models to investigate the role of Tg737 in the hypoxia-enhanced invasion and migration of hepatoma cells. The hepatoma cell lines HepG2 and MHCC97-H were subjected to normoxic or hypoxic conditions, and the cell adhesion, invasion, and migration capabilities were tested. The expression of Tg737 under normoxia or hypoxia was detected using western blot assays; cell viability was determined using flow cytometry. Furthermore, we created HepG2 and MHCC97-H cells that over expressed Tg737 prior to incubation under hypoxia and investigated their metastatic characteristics. Finally, we analyzed the involvement of critical molecular events known to regulate invasion and migration.

Results

In this study, Tg737 expression was significantly inhibited in HepG2 and MHCC97-H cells following exposure to hypoxia. The down regulation of Tg737 expression corresponded to significantly decreased adhesion and increased invasion and migration. Hypoxia also decreased the expression/secretion of polycystin-1, increased the secretion of interleukin-8 (IL-8), and increased the levels of active and total transforming growth factor β 1 (TGF-β1), critical regulators of cell invasion and migration. Moreover, the decrease in adhesiveness and the increase in the invasive and migratory capacities of hypoxia-treated hepatoma cells were attenuated by pcDNA3.1-Tg737 transfection prior to hypoxia. Finally, following the up regulation of Tg737, the expression/secretion of polycystin-1 increased, and the secretion of IL-8 and the levels of active and total TGF-β1 decreased correspondingly.

Conclusions

These data provide evidence that Tg737 contributes to hypoxia-induced invasion and migration, partially through the polycystin-1, IL-8, and TGF-β1 pathway. Taken together, this work suggests that Tg737 is involved in the invasion and migration of hepatoma cells under hypoxia, with the involvement of the polycystin-1, IL-8, and TGF-β1 signaling pathway. Tg737 is a potential therapeutic target for inhibiting the high invasion and migration potential of hepatoma cells in hypoxic regions.

【 授权许可】

   
2012 You et al.; licensee BioMed Central Ltd.

【 图 表 】

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