Koo B S, Lee S H, Kim J M, Huang S, Kim S H, Rho Y S, Bae W J, Kang H J, Kim Y S, Moon J H, Lim Y C
Department of Otolaryngology-Head and Neck Surgery, Cancer Research Institute, Daejeon, Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, Korea.
Oncogene. 2015 Apr 30;34(18):2317-24. doi: 10.1038/onc.2014.174. Epub 2014 Jun 23.
Cancer stem cells (CSCs) have been suggested as responsible for the initiation and progression of cancers. Octamer-binding transcription factor 4 (Oct4) is an important regulator of embryonic stem cell fate. Here, we investigated whether Oct4 regulates stemness of head and neck squamous carcinoma (HNSC) CSCs. Our study showed that ectopic expression of Oct4 promotes tumor growth through cyclin E activation, increases chemoresistance through ABCC6 expression and enhances tumor invasion through slug expression. Also, Oct4 dedifferentiates differentiated HNSC cells to CSC-like cells. Furthermore, Oct4(high) HNSC CSCs have more stem cell-like traits compared with Oct4(low) cells, such as self-renewal, stem cell markers' expression, chemoresistance, invasion capacity and xenograft tumorigeneity in vitro and in vivo. In addition, knockdown of Oct4 led to markedly lower HNSC CSC stemness. Finally, there was a significant correlation between Oct4 expression and survival of 119 HNSC patients. Collectively, these data suggest that Oct4 may be a critical regulator of HNSC CSCs and its targeting may be potentially valuable in the treatment of HNSC CSCs.
癌症干细胞（CSCs）被认为是癌症发生和发展的原因。八聚体结合转录因子4（Oct4）是胚胎干细胞命运的重要调节因子。在此，我们研究了Oct4是否调节头颈部鳞状细胞癌（HNSC）CSCs的干性。我们的研究表明，Oct4的异位表达通过激活细胞周期蛋白E促进肿瘤生长，通过ABCC6表达增加化疗耐药性，并通过slug表达增强肿瘤侵袭。此外，Oct4使分化的HNSC细胞去分化为CSC样细胞。此外，与Oct4低表达细胞相比，Oct4高表达的HNSC CSCs具有更多的干细胞样特征，如自我更新、干细胞标志物表达、化疗耐药性、侵袭能力以及在体外和体内的异种移植致瘤性。此外，敲低Oct4导致HNSC CSCs干性显著降低。最后，Oct4表达与119例HNSC患者的生存率之间存在显著相关性。总体而言，这些数据表明Oct4可能是HNSC CSCs的关键调节因子，靶向作用于Oct4在治疗HNSC CSCs方面可能具有潜在价值。
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