eLife digest | TGF-β reduces DNA ds-break repair mechanisms to heighten genetic diversity and adaptability of CD44+/CD24− cancer cells

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TGF-β reduces DNA ds-break repair mechanisms to heighten genetic diversity and adaptability of CD44+/CD24− cancer cells

eLife digest

Affiliation details

Cold Spring Harbor Laboratory, United States; Stony Brook University, United States; Huntington Hospital, Northwell Health, United States; University of Southern California, United States; Cancer Research UK – Cambridge Institute, University of Cambridge, United Kingdom

A single tumor can be made up of thousands of cancer cells that look and behave differently from one another. This observed diversity arises from changes in the DNA sequence of particular genes, changes in the activity of genes, and the ability of cells to transition between different states. As a result, individual cells within a tumor may react differently to certain anti-cancer drugs: most of the cells may be sensitive to the treatment and die, whereas some might be resistant and survive.

Previous studies on several types of human cancers – including breast, brain and lung cancers – have identified a group of cells called CD44+/CD24- cells that seem to be more aggressive and resistant to therapy than other cancer cells. However, it is currently not known exactly how these CD44+/CD24- cells influence a whole tumor’s resistance to anti-cancer drugs.

Certain cancer cells in tumors are exposed to a signal molecule called TGF-β. CD44+/CD24- cells are unusual in that they are able to produce and release this signal molecule themselves. Pal et al. show that in CD44+/CD24- cells from a human lung cancer cell line, TGF-β decreased the activity of genes responsible for accurately fixing breaks in the CD44+/CD24- cells’ DNA. As a result, these cells made more mistakes than other lung cancer cells when repairing damaged DNA and consequently accumulated additional genetic mutations. Furthermore, tumors containing these cells were more likely to survive treatment with chemotherapy.

The findings of Pal et al. show that the CD44+/CD24- cells exposed to TGF-β had a survival advantage because they were more genetically diverse and therefore better able to adapt to new drug treatments and other changes in their surroundings. Future experiments may explore how to specifically target and kill the CD44+/CD24- cells from tumors.

DOI: http://dx.doi.org/10.7554/eLife.21615.002