Pathway Increases Understanding of Prostate Cancer Development

Researchers recently discovered that the signaling pathway Notch is a driver of prostate cancer metastasis.

Notch signaling is crucial for both tissue development and homeostasis, and in prostate carcinogenesis the pathway is believed to be deregulated.

“Most previous studies on the role that Notch plays in prostate cancer were performed in cultured cells in the laboratory,” said researcher Li Xin. “These studies produced contradictory results. Some studies concluded that Notch was an oncogene, that it promoted cancer development, and others that it was a tumor suppressor gene. To gain a better understanding of Notch in prostate cancer we decided to study its role in an animal model in a defined genetic context.”

Since Pten is a tumor suppressor gene, and there has been a correlation found between its loss of function and prostate cancer progression, researchers used a prostate loss-of-function in a Pten prostate cancer mouse model to find the role of Notch signaling in prostate cancer progression.

“In a human prostate cancer specimen dataset, we found that there is an inverse correlation between the expression level of Pten and the level of Notch activity,” Xin said.

The results of the study showed that Notch activation can be a driver for metastasis to major internal organs, such as the lungs or liver. Further research was conducted to determine the mechanisms of Notch driving metastasis.

“Our major conclusion is that Notch is able to upregulate another molecule called FoxC2, which is very important for the metastatic potential of the cells,” Xin said. “If we suppress FoxC2, we can attenuate Notch-mediated metastatic activity. Future studies will aim to address whether Notch inhibition can suppress tumor metastasis. These studies will serve as solid rationale for treating human prostate cancer with Notch inhibitors.”

The study’s findings were published in The Journal of Clinical Investigation