Endoplasmic Reticulum Stress in Renal Cell Carcinoma

The endoplasmic reticulum is an organelle exerting crucial functions in protein production, metabolism homeostasis and cell signaling. Endoplasmic reticulum stress occurs when cells are damaged and the capacity of this organelle to perform its normal functions is reduced. Subsequently, specific signaling cascades, together forming the so-called unfolded protein response, are activated and deeply impact cell fate. In normal renal cells, these molecular pathways strive to either resolve cell injury or activate cell death, depending on the extent of cell damage. Therefore, the activation of the endoplasmic reticulum stress pathway was suggested as an interesting therapeutic strategy for pathologies such as cancer. However, renal cancer cells are known to hijack these stress mechanisms and exploit them to their advantage in order to promote their survival through rewiring of their metabolism, activation of oxidative stress responses, autophagy, inhibition of apoptosis and senescence. Recent data strongly suggest that a certain threshold of endoplasmic reticulum stress activation needs to be attained in cancer cells in order to shift endoplasmic reticulum stress responses from a pro-survival to a pro-apoptotic outcome. Several endoplasmic reticulum stress pharmacological modulators of interest for therapeutic purposes are already available, but only a handful were tested in the case of renal carcinoma, and their effects in an in vivo setting remain poorly known. This review discusses the relevance of endoplasmic reticulum stress activation or suppression in renal cancer cell progression and the therapeutic potential of targeting this cellular process for this cancer.

Automated summary

The endoplasmic reticulum plays crucial roles in protein production, metabolism homeostasis, and cell signaling. Endoplasmic reticulum stress occurs when cells are damaged and its normal functions are compromised. In renal cancer cells, the activation of endoplasmic reticulum stress pathway is exploited to promote cell survival through rewiring of metabolism, activation of stress responses, autophagy, and inhibition of cell death. However, a certain threshold of endoplasmic reticulum stress activation is required to shift the response from pro-survival to pro-apoptotic outcome. The therapeutic potential of targeting endoplasmic reticulum stress in renal cancer is still poorly understood and further research is needed.