The Notch signaling pathway could be playing a role in the spread of prostate cancer to other organs and tissues, according to recent research, opening a new avenue of treatment using Notch signaling inhibitors.
This specific pathway has been shown to be faulty in several types of cancer, and is an important system mediating communication between neighboring cells. It plays a major role during embryonic development and neural differentiation and function.
“Most previous studies on the role that Notch plays in prostate cancer were performed in cultured cells in the laboratory. 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,” Dr. Li Xin, associate professor of molecular and cellular biology at Baylor College of Medicine, and senior author of the study, said in a press release. “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.”
The team used a mouse model of prostate cancer that failed to express a tumor suppressor gene called Pten in their prostate. Xin’s team had previously found there was an inverse correlation between Notch activity and the expression on the Pten gene. In other words, when the expression of Pten went up, the activity of Notch went down, and vice-versa.
The researchers saw that mice without Pten in their prostate (and therefore with overactive Notch signaling), prostate tumors spread to other major organs such as the lungs and the liver, revealing that Notch signaling could activate tumor spread, or metastasis.
The researchers further showed that Notch signaling was likely driving metastasis by upregulating another molecule called FoxC2. When they blocked FoxC2, the Notch-mediated spread of the tumor was reduced.
“This mouse study demonstrated directly in vivo that increased Notch activity can drive prostate cancer metastasis,” Xin said. “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 research article, “Notch promotes tumor metastasis in a prostate-specific Pten-null mouse model,” is published in the Journal of Clinical Investigation.
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