Disrupting tuft cell development may be a new way to treat deadly lung cancer

Cold Spring Harbor Laboratory (CSHL) Professor Christopher Vakoc’s team discovered a new type of small cell lung cancer in 2018. The cancer comes from cells known as tuft cells. The prognosis for tuft cell lung cancer is extremely poor. Now the Vakoc team has discovered how tuft cells are generated in the body. Disrupting the development of tuft cells may represent a new way to treat this deadly lung cancer.

Tuft cells help protect the body from infection. Named for their bushy tuft, the tuft cells are equipped with taste receptors used to detect invaders. The researchers found that a protein called POU2F3 must bind to OCA-T proteins in order for tuft cells to develop. Interfering with the development of tuft cells in the body is predicted to have minimal side effects, especially in adult lung cancer patients.

The only side effect we would expect if you broke this interaction is that you would lose your tuft cellsexplains Xiaoli Wu, who led the research as a student-in-residence at Stony Brook University at CSHL. That could make patients more vulnerable to infection with certain parasites, such as roundworms. But, Wu notes, “worm infections are usually not a major health risk in adult lung cancer patients undergoing chemotherapy

The way the two proteins work together was surprising, Wu says. “Before our study, POU2F3 was thought to act only in generating normal and cancerous tuft cells. The surprise that came from our study is that POU2F3 has an equally important partner to perform this crucial task,” she explains.

The discovery of this protein interaction suggests that better, more targeted therapies may be within reach of tuft cell lung cancer. “The interaction we discovered may be an Achilles heel of these tumors,” Wu says. It also lays the foundation for future research into tuft cell cancer.

This publication will be a starting point for my future research. Our study raises many important questions about tuft cell biology that I will continue to study in the next phase of my scientific career.”


Xiaoli Wu

Source:

Cold Spring Harbor Laboratory

Reference magazine:

wu xs, et al. (2022) OCA-T1 and OCA-T2 are co-activators of POU2F3 in the tuft cell line. Nature. doi.org/10.1038/s41586-022-04842-7.

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