U.K. team links cancer cell shape, gene expression and clinical outcomes

Understanding the relationship between the shifting shape of cancer cells, changes in gene expression, and clinical outcomes could improve understanding of cancer as well as treatment.

Cancer cells are continually changing shape in response to their surrounding environment. Scientists at the Institute of Cancer Research in London have created “maps” linking this shape-changing to alterations in gene expression and real-world outcomes in breast cancer.

To make their maps, the team looked at a data set with cell-shape measurements for more than 307,000 cells over 18 different breast cancer cell lines, as well as a data set containing the expression of more than 28,000 genes for the same cell lines, according to a statement.

They found that changes in cell shape, which can be caused by physical pressure on the tumor, are reflected in shifts in gene activation. Using their maps, researchers analyzed thousands of samples from nearly 2,000 breast cancer patients, discovering that shape-driven changes in gene expression are related to clinical outcomes.

In particular, the team found that the protein NF-kappaB could promote the growth and spread of cancer cells. This protein is “rarely faulty” in solid tumors, and mechanical forces in the environment surrounding the tumor are involved in causing cell shape to change and switching the NF-kappaB gene on, the scientists determined.

The maps could eventually be used to help guide treatment decisions, tailor therapy to individual patients and improve outcomes.

“Understanding the links between how a breast cancer looks and acts, alongside its genetic makeup, will help researchers develop a more detailed picture of the disease,” said Karen Vousden, chief scientist at Cancer Research UK, which funded the research.

“The insights and approaches used in this research could one day lead to us being able to tell from appearance, how aggressive someone's cancer is and how likely to spread, helping doctors decide the best course of treatment,” she said.

In other gene-centered approaches, University of Miami researchers have inhibited HDACs, enzymes that regulate gene expression, to target and attack breast and ovarian cancer stem cells. Meanwhile, a team from Imperial College London discovered that boosting the expression of a particular microRNA in aggressive breast cancer cells silenced three genes, and that doing the same in mouse models prevented the spread of cancer.