Jess Hebert, PhD

Metastasis is the spreading of a cancer from where it first develops to other parts of the body. Metastatic cancer is very difficult to treat because metastases can be very small and disperse all throughout the body, which means that they cannot all be surgically removed. As a result, metastatic cancer must be treated with drugs, which are currently not very effective. Indeed, metastasis causes the majority of all cancer deaths, including lung cancer. Accordingly, there is a great need to develop a better understanding of metastatic cancer to enable the development of new therapies to treat cancers once they have metastasized. Our research has shown that the gene Cdkn2a normally helps to suppress metastasis. We will study exactly how the loss of Cdkn2a enables a cancer to spread aggressively. This knowledge could be critical for the development of future therapies to prevent the spread of cancer or eliminate metastatic cancer anywhere.

Update: We have found that inactivation of the gene Cdkn2a can lead to aggressive metastasis in lung cancer. The Cdkn2a gene can create two different proteins: p14ARF and p16INK4a. By selectively inactivating either protein individually, we found that both are critical in regulating metastasis. To understand how Cdkn2a controls metastasis, we also performed single-cell RNA sequencing of both primary and metastatic cancer cells with inactivation of Cdkn2a. This provided a snapshot of all the genes being expressed in every cell (their “cell state”). We observed that metastatic cells without Cdkn2a had diverged substantially from their origins as lung epithelial cells, compared to primary cancer cells. We are continuing to explore how Cdkn2a loss creates this cell state and promotes metastasis.