Epigenetic Shifts Drive Pancreatic Cancer Spread

Johns Hopkins researchers find gene KLF5 fuels growth of metastatic pancreatic tumors through epigenetic changes, not DNA mutations.

Published on Feb. 11, 2026

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In a lab-grown cell study, Johns Hopkins Medicine scientists report they have found that a gene called KLF5 (Krueppel-like factor 5) fuels the growth of spreading pancreatic tumors not by acquiring abnormal changes in the cancer cells' DNA code itself, but by altering chemical changes and organization of DNA, or epigenetics, that turns genes on and off.

Why it matters

The findings suggest that epigenetic alterations, rather than DNA mutations, may be a major driver of pancreatic cancer metastasis, and that targeting the KLF5 gene could be a promising approach for developing new treatments to halt the spread of this deadly cancer.

The details

The researchers used CRISPR gene-editing technology to silence various genes in pancreatic cancer cells and found that turning off KLF5 had the greatest impact on reducing the growth and invasion of metastatic cells. They also discovered that KLF5 controls the tight packaging of DNA, an epigenetic factor that enables genes to be turned on or off. Additionally, KLF5 was found to regulate two other epigenetic modifier genes, NCAPD2 and MTHFD1, in metastatic but not primary pancreatic cancer cells.

  • The current study, funded in part by the National Institutes of Health, was described today in Molecular Cancer.

The players

Andrew Feinberg

M.D., Bloomberg Distinguished Professor in the Johns Hopkins University schools of medicine, engineering and public health, and the lead researcher on the study.

Kenna Sherman

A graduate student in the Johns Hopkins Human Genetics and Genomics program and the first author of the study.

Johns Hopkins Medicine

The institution where the research was conducted.

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What they’re saying

“Epigenetic alterations are underappreciated as a major route to developing and fueling the growth of cancer metastasis.”

— Andrew Feinberg, M.D., Bloomberg Distinguished Professor (Molecular Cancer)

“This could suggest that, to develop treatments for pancreatic cancer metastasis, the gene may not need to be entirely shut down to have a positive effect.”

— Andrew Feinberg, M.D., Bloomberg Distinguished Professor (Molecular Cancer)

“We are adding to evidence that cancer metastases are not caused by additional mutations in the primary cancer, but by additional epigenetic changes, enabling the cancer to thrive and grow.”

— Kenna Sherman, Graduate student (Molecular Cancer)

What’s next

Several anti-cancer compounds targeting KLF5 are in development, and the researchers plan to further investigate the role of epigenetic changes in driving pancreatic cancer metastasis.

The takeaway

This study provides important insights into the epigenetic mechanisms underlying pancreatic cancer metastasis, suggesting that targeting the KLF5 gene and other epigenetic regulators may be a promising approach for developing new treatments to halt the spread of this deadly disease.