How metastatic colorectal cancer progresses to the liver

Liver metastasis is the primary cause of colorectal cancer deaths, with almost 70% of the patients developing a liver tumor. The recent revelation of low levels of protein kinase C zeta (PKC zeta) in distant metastasis and colorectal cancer cells have not been able to show how this aids in the poor prognosis and spread of tumors in patients.

A new study helps in explaining the connection between metastatic colorectal cancer and PKC zeta. Deficiency of PKC zeta promotes liver metastasis by inactivating an enzyme known as ADAR2 and subsequently secreting molecules called miR-200s into the blood from cancer cells.

• Furthermore, it was discovered that there was a significant reduction of liver metastasis in mice with colorectal cancer when treatment with a compound that inhibits secretion of miR-200s was administered.

• Findings suggest that increased blood levels of miR-200s can serve as a non-invasive diagnostic marker for patients at metastasis risk.

• A previous study had pinpointed that PKC zeta was a tumor suppressor in colorectal cancer. It was found that cancer cells would survive and proliferate when deprived of nutrients because losing PKC zeta.

• Evidence shows that dysregulated miRNAs (molecules that regulate gene activity) result to sustained proliferation, metastasis and resistance of cell death.

Understanding mechanisms that control miRNAs will help in designing better strategies for treating metastasis. Colorectal cancer patients with tumors that are metastatic have high blood levels of vesicles that contain miR-200s. The mice with colorectal cancer that were injected with a compound that inhibits miR-200s secretion were found to have significantly reduced liver metastasis. There is the need to identify signaling vulnerabilities that are unleashed when tumor suppressors are inactivated. It will establish the signals derived from PKC zeta that are controlling the miR-200s as potential therapeutic targets in cancer metastasis.