Mechanism of endoplasmic reticulum stress and tumor progression in renal cell carcinoma

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In renal cell carcinoma (RCC), it was reported that HIF-VEGF signaling pathway could be under the control of endoplasmic reticulum stress (ER stress). Strong expression of GRP78 was also reported to play an important role in ER stress for RCC. In 2010, we investigated the relationship between expression level of GRP78 and clinicopathological parameters using RCC specimens. Statistically significant association was found between GRP78 positivity and higher tumor grade, advanced T stage, lymphovascular invasion, regional nodal involvement, and distant metastasis. Positivity of GRP78 expression was significantly associated with shorter disease-specific and progression-free survival.Representative RCC cell lines such as Caki-1, 786O, A498, 769P showed strong expression of GRP78 and IRE1 among ER stress-related proteins. It seemed that the expression of HIF1 and HIF2 were influenced by that of IRE1. So far, inhibition of GRP78 and IRE1 could lead to more anticancer effect on RCC cells.