Bladder cancer is a rare form of cancer, with a relatively high recovery rate. Recurrence is still an issue; however, with around half of patients affected. Prognostic tests can help identify patients who have a high likelihood of recurrence before it occurs. Using this information, doctors can take preventative measures and increase the overall survival rate of patients.
A team from Taiwan decided to tackle this task, focusing on identifying possible transcription factors that might influence tumor progression. Previous work has shown transcription factors tied to the differentiation of cells in adults may also have pro-tumor effects. They analyzed a series of these transcription factors in bladder cancer to identify any that correlate with recurrence-free survival (RFS). Sex determining region Y box-2 (SOX2) was found to be the only transcription factor tested that had a strong correlation.
Normally SOX2 is a transcription factor involved in the maintenance of undifferentiated cells. It had been implicated in recent work to be a possible pro-tumor factor in some cancers. SOX2 was tested to identify its role in cell survival using two bladder cancer cell lines, one with high SOX2 expression and one with low expression. They found that a low SOX2 expression led to a reduction in cellular proliferation. Following this discovery, they focused their testing on the AKT pathway and if SOX2 affected it. This pathway is involved in cellular proliferation, and its abnormal activation is common in many cancers. The analysis showed that high levels of SOX2 correlated with high levels of AKT activation in bladder cancer.
The group then examined the genetic expression of SOX2 overexpressing bladder cancer cells versus normal expressing bladder cancer cells. Insulin like growth factor 2 (IGF2), a peptide hormone whose overexpression in other cancers is linked to an aggressive phenotype, was found to increase and decrease with SOX2 levels. Importantly, IGF2 signaling was vital in the cellular proliferation affects SOX2 generated. This effectively connects SOX2 to two separate pro-tumor factors, AKT activation, and IGF2 levels, which make it a good target for further biomarker studies.
This work identified SOX2 as a possible biomarker that can be used to predict the prognosis of bladder cancer patients. Furthermore, SOX2’s connection to both AKT and IGF2 makes it a potential therapeutic target for future research. SOX2 is already being studied in several other cancers, including lung and breast cancers. With further investigation, it may prove to be a good target for prognostic tests and increase the survival of patients diagnosed with bladder cancer.
Sources: Nature, Cell Signaling Technologies, Inc.
