Researchers from UCL, the Wellcome Sanger Institute, and the University of Cambridge have discovered the “cell of origin” for lung squamous cell carcinoma (LUSC), the second most common lung cancer. Published in Science, the study reveals how specific basal cells in the trachea become dominant and spread, eventually forming tumors. The findings could lead to earlier detection and prevention strategies for this deadly disease.
The study focused on basal cells expressing the gene Krt5, which are found in the trachea. In experiments with mice and human samples, the team observed that these cells, when exposed to carcinogens like those in tobacco smoke, multiplied aggressively and invaded the lungs. Over time, they displaced normal cells, creating precancerous lesions that can develop into LUSC.
Single-cell RNA sequencing showed that as these damaged basal cells expanded, a transitional cell population expressing Krt13 became more abundant, while protective luminal cells declined. The researchers also found that precancerous lesions in human smokers often originated from the same damaged basal cell, even when appearing in different parts of the lungs.
Professor Sam Janes, senior author, explained, “By understanding the ‘cell of origin’ and how these changes begin, we aim to design strategies to prevent lung cancer or detect it much earlier.” Dr. Sandra Gómez-López added, “Our experiments show how disrupted cell balance from smoking leads to dominant, cancer-prone cell populations.”
The study highlights the potential for early intervention by targeting the identified cell populations. Future research could lead to new diagnostic tests or treatments to halt the progression of LUSC, offering hope for reducing the global burden of lung cancer, which remains the leading cause of cancer-related deaths.
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