![]() On the other hand, patients with high levels of SOX1 in lower grade glioma had better outcomes (Supplementary Fig. Unexpectedly, patients with high levels of SOX1 expression in several cancer tissues had a poorer prognosis, as compared to those with low levels of SOX1 (Supplementary Fig. Therefore, these genes may be re-classified as “tumor hypnotists” attributing to their dynamic roles in different tumor micro-environments. The term “tumor suppressor” suggests that the genes have inhibitory effects on cancer cells proliferation, nevertheless, some of these genes in turn favors cancer cells survival under therapeutic interventions. In the current study, we present a new model that mimics QCC by overexpression of SOX1 in NPC cells. SOX1, a transcription factor that primarily functions in neurogenesis, has been shown to act as a tumor suppressor in several cancer types, including NPC. However, the intrinsic factors regulating QCCs, independent of extracellular environmental cues, remain unknown. Various intracellular markers, such as Ki-67, c-Myc, Cyclin D, p27Kip1, or Rb, have been applied to detect the quiescent state of cancer cells, while most in vitro models of QCCs rely on alteration of tumor micro-environment, such as nutrient deprivation, hypoxia, contact inhibition, or anti-cancer treatment. To tackle this challenging problem, numerous studies have focused on the mechanisms that regulate initiation and termination of cell quiescence. Moreover, QCCs can re-enter the cell cycle and proliferate, leading to cancer progression and metastasis. Thus, gaining a comprehensive understanding of the mechanisms of NPC chemoresistance is crucial.Ĭurrent study indicates that quiescent cancer cells (QCCs) may be responsible for NPC recurrence, as QCCs are dormant for long periods of time and account for resistance to conventional cancer treatments. ![]() However, chemoresistance poses a significant challenge to the successful therapy in NPC, as 10–20% of patients experience recurrence after initial treatment, with 70–80% of recurrent NPC cases being locally advanced. Nasopharyngeal carcinoma (NPC) is a prevalent disease in Southern China and Southeast Asian countries, with concurrent chemoradiotherapy being a key treatment option. Basing on the dynamic role of SOX1 in different stages of cancer development, SOX1 would be regarded as a “tumor hypnotist”. Our study presents an evolutionary trade-off between tumor growth and chemoresistance orchestrated by SOX1-MYC in NPC. ![]() When switching to a paclitaxel-free culture environment, the cells with decreased levels of SOX1 re-express MYC, resulting in increased abundance of proliferative cancer cells. ![]() Moreover, SOX1 directly binds to the promoter region of the MYC gene, leading to transcriptional suppression. The chemotherapy resistance induced by SOX1 can not pass to next generation, as the cells that undergo re-proliferation become sensitive to paclitaxel again. However, once SOX1 expression is decreased, the NPC cells recover and enter a proliferative state. These cells maintain a quiescent state with decreased translational activity and down-regulated cell growth potential. ![]() Using a model that mimics therapeutic resistance and tumor recurrence, a subpopulation of SOX1-induced NPC cells is refractory to paclitaxel, a cell cycle-specific chemotherapy drug. In this study, we show that SOX1 induces nasopharyngeal carcinoma (NPC) cells to enter a quiescent state. However, high expression of SOX1 in late-stage head and neck squamous cell carcinoma leads to poor prognosis. SOX1, a well-known tumor suppressor, delays malignant progression in most cancer types. ![]()
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