SOX1 acts as a tumor hypnotist rendering nasopharyngeal carcinoma cells refractory to chemotherapy

Abstract

Abstract SOX1 delays tumor progression in most non-brain cancers and is regarded as a tumor suppressor. However, head and neck squamous cell carcinoma patients with high expression levels of SOX1 are inclined to experience recurrence after initial therapy and suffer from poor prognosis. Here, we first report that an intrinsic transcription factor SOX1 induces individual nasopharyngeal carcinoma (NPC) cells to enter a quiescent state. We applied a model to mimic the process of therapeutic resistance and tumor recurrence in clinical. In a stressful culture environment, a subpopulation of SOX1-induced NPC cells was refractory to paclitaxel, a cell cycle-specific chemo drug. After treatment with chemotherapeutics, NPC cells with high levels of SOX1 maintained the quiescent state, with characteristics of low activity in protein synthesis and down-regulated cell growth signaling. Once SOX1 expression was decreased, the NPC cells could recover to a proliferative state. As cell cycle-specific chemotherapeutics targeted the proliferative state of cells, SOX1-induced drug resistance couldn’t be inherited in the reactivated NPC cells. When switching to a stress-free culture environment, the decreased SOX1 lost its transcriptional function and re-expressed MYC, a critical gene controlling cell growth. Proliferative NPC cells with low levels of SOX1 would form the dominant population again. Our study demonstrates an evolutionary trade-off between tumor progression and chemoresistance orchestrated by MYC and SOX1 in NPC. According to the dynamic role of SOX1 in different stages of cancer development, we suggest sorting SOX1 as “tumor hypnotist” instead of “tumor suppressor”.