Stress protein in fibroblasts may be a good target for future cancer drugs

A Penn study finds the ATF4 protein is overactive in many types of tumor cells and tumor-supporting fibroblasts to promote tumor survival, and may be a good target for future cancer treatments.

A stress protein that is overactive in many types of tumor cells also has a key role in tumor-supporting cells called fibroblasts, and may be a good target for future cancer treatments, suggests a study from researchers at the Perelman School of Medicine.

Microscopic view of fibroblasts.


The researchers, whose findings appear in Nature Cell Biology, discovered in experiments in animal models of pancreatic cancer and melanoma that the stress protein, known as ATF4, enables fibroblasts to support tumor growth by promoting the formation of tumor-serving blood vessels. Deleting ATF4 in fibroblasts severely impaired new tumor-supportive vessel formation as well as tumor growth, without causing significant harm to the mice, the researchers found.

“Our results suggest that inhibiting ATF4 could work against many types of cancer, and we’re now actively pursuing that strategy,” says study senior author Constantinos Koumenis, the Richard H. Chamberlain Professor of Research Oncology in the department of Radiation Oncology.

Underscoring the likely relevance of their results to human cancers, the researchers found that in tumor tissue from human pancreatic cancer and melanoma patients there is a significant correlation between markers of ATF4 activity and markers of collagen production. Moreover, in the melanoma cases, higher collagen production correlated with worse prognoses.

Read more at Penn Medicine News.