October is Breast Cancer Awareness Month. But at the Weizmann Institute, the focus on defeating this pervasive cancer is front and center every day, all year long.
Now, in exciting news, researchers at Weizmann, in collaboration with the National Cancer Institute in the U.S. and other institutions, have revealed a mechanism that accounts for the spread of a particularly aggressive type of breast malignancy. Cancers that spread rapidly are generally harder to treat, but clarifying the molecular basis of such aggressive cancers may lead to new drugs for treating these fast-growing malignancies.
The study began with a large-scale computational analysis of data from several databases, including information on patient survival and the genes that are overly active in fast-spreading cancers. The scientists came up with a list of some 20 genes that the most aggressive breast cancers appeared to need in order to spread. The top two are genes that play a role in cell division, and they already serve as targets for anticancer drugs. But the third gene puzzled researchers: It encoded a protein called NUP93, one of the numerous components of the pores, or tunnel-like structures, in the envelope enclosing a cell’s nucleus.
The researchers found that NUP93 was present in abnormally large amounts in breast cancer patients with the poorest survival records. As the disease progressed, the genomes of some of these patients came to contain two or three copies of the gene for NUP93 instead of the usual one. Strikingly, many of these patients had tumors that were not sensitive to estrogen. Such tumors, which make up about a third of all breast cancers, are particularly difficult to treat because they lack the estrogen receptors that are targeted by hormonal anticancer drugs.
“Understanding what drives such cancers is especially crucial because currently, our means of treating them are limited,” says Prof. Yosef Yarden of Weizmann’s Biological Regulation Department, who headed the research team.
The team confirmed that there is indeed a connection between large amounts of NUP93 and the aggressiveness of cancer. The scientists discovered that the NUP93 protein forms a tunnel in the nuclear membrane, allowing the passage of proteins called importins. This process enables the cancer to get access to the cell’s genome, where it increases the cell’s ability to migrate and spread the disease.
“The cancer needs an express highway to the nucleus, so that growth signals from the outside can quickly reach the genome,” Yarden explains. “The more NUP93 tunnels there are on the way, the faster the signals can travel, and the greater the metastasis in the patient’s body.”
Since metastasis is the main force leading to death in patients with breast cancer, disrupting this process is a promising new avenue for developing potential therapies.
