Researchers at Johns Hopkins Medicine have found a gene that helps pancreatic cancer move around the body. The gene is called KLF5.
In lab tests, KLF5 did not change the DNA letters. Instead, it changed how the DNA is packed and marked. These changes decide which genes are turned on or off.
"Changes that do not alter the DNA code can still drive cancer spread," says Dr. Andrew Feinberg, a professor at Johns Hopkins.
His team showed in 2017 that most pancreatic tumors have many of these non‑DNA‑changing changes. Those changes, not new mutations, seemed to help the cancer travel.
The new study, published in Molecular Cancer and supported by the NIH, builds on that work and suggests new ways to treat the disease.
CRISPR Test Finds the Most Important Gene
The scientists used CRISPR, a tool that can turn off specific genes. They switched off many genes, one by one, to see which stopped cancer cells from growing.
KLF5 was the strongest driver. When it was active, cancer cells grew faster and spread more. In patient samples, 10 out of 13 people had higher KLF5 activity in at least one metastatic tumor compared with their original tumor.
KLF5 Controls DNA Packing and Gene Activity
Further tests showed that KLF5 changes how tightly DNA is wrapped inside the cell. Tighter or looser packing decides which genes can work.
Even a small rise in KLF5 made cancer cells grow a lot. "We may not need to shut the gene completely to help patients," says Feinberg. He notes that several experimental medicines aimed at KLF5 are already being tested.
Other Genes Linked to Spread
The study also found that KLF5 controls other genes, such as NCAPD2 and MTHFD1, but only in metastatic cancer cells, not in the original tumors grown in the lab. These genes act as epigenetic modifiers, adding chemical tags that change DNA structure.
Funding and Team
The work was funded by the National Institutes of Health, a Celgene License Pathway Agreement, and a donation from friends and family of Jasmine Lampadarios.
Team members included Masahiro Maeda, Weiqiang Zhou, Jiaqi Cheng, Yuta Nihongaki, Adrian Idrizi, Rakel Tryggvadottir, Oscar Camacho, Michael Koldobskiy, Barbara Slusher, Hongkai Ji (Johns Hopkins), Xingbo Shang and Andre Levchenko (Yale), and Jimin Min and Anirban Maitra (NYU Langone Health).