Stem Cell Quiescence Acts as a Tumor Suppressor in Squamous Tumors

The study from December 15, 2013, investigated the role of hair follicle stem cell (HFSC) quiescence in preventing tumor formation in squamous tissues. It was found that HFSCs could not initiate tumors during their quiescent phase, indicating that stem cell quiescence serves as a tumor suppressor in cutaneous squamous cell carcinoma (SCC). The activation state of HFSCs was critical for tumorigenesis, with tumors forming only when HFSCs exited quiescence. The tumor suppressor Pten was essential for maintaining this quiescent-based tumor suppression, as its deletion led to tumor formation without affecting cell proliferation. Experiments showed that hyperplasias induced by KrasG12D occurred only during the transition from telogen to anagen, not during quiescence, even up to ten weeks post-induction. A strong correlation between the active phase of the hair cycle and SCC in human skin was also observed. The study involved experiments with 3 to 5 mice and quantified up to 1,361 hair follicles in some tests. Additionally, the loss of both Pten and p53, with KrasG12D expression, was sufficient to drive skin malignancies in quiescent HFSCs, resulting in various types of skin tumors. The study highlighted the importance of Pten in maintaining HFSC quiescence and the tumor-suppressive role of stem cell quiescence, especially in organs with cyclical stem cell turnover or activation by injury.