Abstract 3125: SOX2 controls the tumor initiation and development and acts as a prognostic predictor of oral squamous cell carcinoma

Abstract

Abstract Background: Sex determining region Y-BOX2 (SOX2), a regulator of the self-renewal ability of stem cells, plays a compelling role in initiation and development of cancer. However, little is known about the role and network controlling of SOX2 in oral squamous cell carcinoma (OSCC) development. Method: In this study, we conducted a retrospective cohort of 229 OSCC patients from two independent Chinese centers from May 2003 to August 2012. SOX2 expression in these samples was determined by immunostaining. Univariate and multivariate analyses were performed. Then we generated SOX2-creERT2 mice that expressing an inducible Cre recombinase under the control of a minimal promoter of SOX2, along with a tdTomato reporter. These mice were exposed to low dose 4NQO in the drinking water either for 8, 12 or 16 weeks. We further investigate the network controlling of SOX2 by ChIP assay. Then we detected the expression of SOX2 in response to AFF4 knockdown and overexpression by western blot, respectively. Furthermore, we used wound-healing, transwell, sphere formation and limiting dilution assay to confirm whether SOX2 expression was regulated by AFF4. Results: In the multiple cohorts, high SOX2 protein expression was negatively correlated with the overall survival for OSCC patients. Impressively, we found chemotherapy only improved outcomes of patients with low SOX2 expression, but very limited effects to high SOX2 expression patients. Meanwhile low SOX2 expression patients had significantly better survival with rather than without chemotherapies. Lineage tracing study in vivo suggested that SOX2 positive cells play an important role in the carcinogenesis of OSCC as epithelial stem cells. Increasing SOX2 positive cells and their daughter cells was a major trigger in the initiation of OSCC. Mechanistically, we found SOX2 was regulated by AFF4, the core component of Super elongation complex (SEC) to promote the proliferation, migration and invasion of OSCC cells. SOX2 expression changed in parallel with AFF4 expression in response to depletion and overexpression of AFF4, respectively. More importantly, the inhibited proliferation, migration, invasion and ALDH activity induced by knockdown of AFF4 in OSCC cells were rescued by overexpression of SOX2. Conclusion: Collectively, our findings indicate SOX2 acts as a prognostic predictor and controls the tumor initiation and development in oral squamous cell carcinoma. SOX2 may serve as a potential target of therapies for patients with OSCC. Note: This abstract was not presented at the meeting. Citation Format: ZIHAO WEI, FENGYING YIN, PENG DENG, XUEFENG ZHANG, JING DENG, JING LI, LIANG XIE, QIANMING CHEN. SOX2 controls the tumor initiation and development and acts as a prognostic predictor of oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3125.