The shortage of oxygen, which terms as hypoxia, plays critical roles in many cancers. But limited is known about the mechanism of hypoxia stress on the tumorigenesis. Understanding the mechanism can help the clinical treatment to many tumors. Recently, LIU Jiang’s lab from Beijing Institute of Genomics, Chinese Academy of Sciences (BIG) in collaboration with the University of Chicago, revealed that speckle-type POZ protein (SPOP) acts as the key regulatory hub in hypoxia induced tumorigenesis in kidney cancer.  

Under normal physiological conditions, hypoxia stress can promote the expression of PDGF and EGF, which in turn can promotes the angiogenesis. Therefore, many investments have been focused on the inhibiting the receptors of PDGF and EGF to treat the cancer patients. However, the clinical outcome is very limited, suggesting that more important targets are required to be identified.  

Hypoxia induced factors have been found elevated in nearly 50% of kidney cancers. Surgical operation is the major treatment to kidney cancer, but it is not suitable to the patients with metastasis. Those patients need the drug to cure their cancers. Unfortunately, the clinical outcome from the current drugs is very poor. Therefore, scientists used kidney cancer as the model to understand the mechanism of the tumorigenesis under hypoxia stress. Their study unravels that hypoxia stress can elevate the expression of SPOP, and drive the cytoplasmic accumulation of SPOP, which is sufficient to induce the tumorigenesis. Scientists further revealed that SPOP, an E3 ligase adaptor, can degrade the tumor suppressor PTEN, ERK phosphatases and many other proteins, which can cause the kidney tumorigenesis. 

Since the accumulation of SPOP in the cytoplasm plays the crucial roles in kidney cancer, scientists are interested whether the inhibition of SPOP can kill the tumor. Their studies show that the deletion of SPOP can only kill cancer cell, but not the normal cells, suggesting that SPOP could be a promising therapeutic target specific to cancer. In the future, success in the drug target to SPOP will benefit many cancer patients, not only kidney cancer patients, but also many other cancers patients.  

The work was supported by CAS, Ministry of Science and Technology and Natural Science Foundation of China. The article has been online published by Cancer Cell on Mar 20, 2014.