Stem cell quiescence acts as a tumor suppressor mechanism in hair follicle initiated squamous tumors

In many organs, adult stem cells are uniquely poised to serve as cancer cells of origin. In the epidermis, hair follicle stem cells (HFSCs) cycle through stages of quiescence (telogen) and proliferation (anagen) to drive hair growth. Within the hair follicle, HFSCs are capable of initiating squamous cell carcinoma, yet it is unclear how the hair cycle contributes to tumorigenesis. The data presented here show that HFSCs are unable to initiate tumors during the quiescent phase of the hair cycle, indicating that the mechanisms that keep HFSCs dormant are dominant to gain of oncogenes (Ras) or loss of tumor suppressors (p53). Instead, prolonged oncogenic stimuli only exert their effects when HFSC quiescence mechanisms are removed by normal HFSC activation. Furthermore, Pten activity is necessary for quiescence based tumor suppression, since Pten deletion alleviates this stem cell specific ability without affecting proliferation per se. Overall design: Small RNAs were cloned from Trizol-lysed cells sorted from mouse skin and sequenced with the Illumina HiSeq2000.

3

White AC, Khuu JK, Dang CY, Hu J, Tran KV, Liu A, Gomez S, Zhang Z, Yi R, Scumpia P, Grigorian M, Lowry WE