Neuronal molecule that make prostate cancer more aggressive identified in recent study

Prostate cancer is the second most common cancer and the second leading cause of cancer death among American men. Now, researchers have discovered key molecular players that drive prostate cancer to progress into a highly aggressive form of the disease called neuroendocrine prostate cancer that currently has no effective treatment. The finding uncovers new avenues to explore for therapeutics to treat neuroendocrine prostate cancer.

To better understand how neuroendocrine prostate cancer develops, Dr. Languino and colleagues looked for biomarkers of the disease. To look for molecules unique to neuroendocrine prostate cancer, the researchers found that aVb3 integrin expression in prostate cancer cells bumped up the expression of a known marker of neuroendocrine prostate cancer and significantly increased the expression of a molecule called Nogo receptor 2 (NgR2). Dr. Languino and her colleagues wanted to find out what this molecule, a neuronal protein, is doing in cancer.

An initial experiment revealed that NgR2 binds the aVb3 integrin. The scientists also saw that in mice with neuroendocrine prostate tumors, aVb3 integrin and NgR2 were both present in the primary tumor and in cancerous lesions that had formed in the lungs of the animals. A follow-up experiment made it clear that both aVb3 integrin and NgR2 are necessary for neuroendocrine prostate cancers. When Dr. Languino and her team lowered the amount of NgR2 in neuroendocrine prostate cancer cells, neuroendocrine markers also decreased. The results suggest that NgR2 plays a role in the development of neuroendocrine prostate cancer.

Reference:

Fabio Quaglia, Shiv Ram Krishn, Khalid Sossey‐Alaoui, Priyanka Shailendra Rana, Elzbieta Pluskota, Pyung Hun Park, Christopher D. Shields, Stephen Lin, Peter McCue, Andrew V. Kossenkov, Yanqing Wang, David W. Goodrich, Sheng‐Yu Ku, Himisha Beltran, William K. Kelly, Eva Corey, Maja Klose, Christine Bandtlow, Qin Liu, Dario C. Altieri, Edward F. Plow and Lucia R. Languino (2022) “The NOGO receptor NgR2, a novel αVβ3 integrin effector, induces neuroendocrine differentiation in prostate cancer,” Scientific Reports, 12:18879 https://doi.org/10.1038/s41598-022-21711-5